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Background The broad antibacterial spectrum of piperacillin/tazobactam makes the combination suitable for the treatment of nosocomial bacterial central nervous system (CNS) infections. As limited data are available regarding piperacillin CNS exposure in patients without or with low-grade inflammation, a clinical study was conducted (1) to quantify CNS exposure of piperacillin by cerebral microdialysis and (2) to evaluate different dosing regimens in order to improve probability of target attainment (PTA) in brain. Methods Ten acute hemorrhagic stroke patients (subarachnoid hemorrhage, n = 6; intracerebral hemorrhage, n = 4) undergoing multimodality neuromonitoring received 4 g piperacillin/0.5 g tazobactam every 8 h by 30-min infusions for the management of healthcare-associated pneumonia. Cerebral microdialysis was performed as part of the clinical neuromonitoring routine, and brain interstitial fluid samples were retrospectively analyzed for piperacillin concentrations after the first and after multiple doses for at least 5 days and quantified by high-performance liquid chromatography. Population pharmacokinetic modeling and Monte Carlo simulations with various doses and types of infusions were performed to predict exposure. A T>MIC of 50% was selected as pharmacokinetic/pharmacodynamic target parameter. Results Median peak concentrations of unbound piperacillin in brain interstitial space fluid were 1.16 (range 0.08–3.59) and 2.78 (range 0.47–7.53) mg/L after the first dose and multiple doses, respectively. A one-compartment model with a transit compartment and a lag time (for the first dose) between systemic and brain exposure was appropriate to describe the brain concentrations. Bootstrap median estimates of the parameters were: transfer rate from plasma to brain (0.32 h−1), transfer rate from brain to plasma (7.31 h−1), and lag time [2.70 h (coefficient of variation 19.7%)]. The simulations suggested that PTA would exceed 90% for minimum inhibitory concentrations (MICs) up to 0.5 mg/L and 1 mg/L at a dose of 12–16 and 24 g/day, respectively, regardless of type of infusion. For higher MICs, PTA dropped significantly. Conclusion Limited CNS exposure of piperacillin might be an obstacle in treating patients without general meningeal inflammation except for infections with highly susceptible pathogens. Brain exposure of piperacillin did not improve significantly with a prolongation of infusions. Electronic supplementary material The online version of this article (10.1007/s12028-020-00947-x) contains supplementary material, which is available to authorized users.

Purpose To describe 5-fluorouracil (5FU) pharmacokinetics, myelotoxicity and respective covariates using a simultaneous nonlinear mixed effect modelling approach. Methods Thirty patients with gastrointestinal cancer received 5FU 650 or 1000 mg/m2/day as 5-day continuous venous infusion (14 of whom also received cisplatin 20 mg/m2/day). 5FU and 5-fluoro-5,6-dihydrouracil (5FUH2) plasma concentrations were described by a pharmacokinetic model using NONMEM. Absolute leukocyte counts were described by a semi-mechanistic myelosuppression model. Covariate relationships were evaluated to explain the possible sources of variability in 5FU pharmacokinetics and pharmacodynamics. Results Total clearance of 5FU correlated with body surface area (BSA). Population estimate for total clearance was 249 L/h. Clearances of 5FU and 5FUH2 fractionally changed by 77%/m2 difference from the median BSA. 5FU central and peripheral volumes of distribution were 5.56 L and 28.5 L, respectively. Estimated 5FUH2 clearance and volume of distribution were 121 L/h and 96.7 L, respectively. Baseline leukocyte count of 6.86 × 109/L, as well as mean leukocyte transit time of 281 h accounting for time delay between proliferating and circulating cells, was estimated. The relationship between 5FU plasma concentrations and absolute leukocyte count was found to be linear. A higher degree of myelosuppression was attributed to combination therapy (slope = 2.82 L/mg) with cisplatin as compared to 5FU monotherapy (slope = 1.17 L/mg). Conclusions BSA should be taken into account for predicting 5FU exposure. Myelosuppression was influenced by 5FU exposure and concomitant administration of cisplatin.

The present study was planned to assess the distribution of tuberculosis in children and evaluate the antimycobacterial sensitivity pattern of Mycobacterium tuberculosis (MTB) isolates from pediatric patients. A total number of 1718 pediatric patients suspected of Mycobacterium tuberculosis were enrolled in the Institute of Child Health and Children's Hospital, Lahore during 2016-17. Out of 1718, only 710 different types of samples were tested for MTB. The samples were processed using bacteriology and GeneXpert along with the chest X-ray and clinical picture of the patients. The sensitivity pattern of Streptomycin, Isoniazid, Rifampicin and Ethambutol (SIRE) was determined using BACTEC MGIT 960. Total patients were divided into four groups including group A (birth to 12 months), B (1 to 5 years), C (6 to 10 years), and D (11 to 15 years). Out of 710, 106 (55 females and 51 males) were declared positive and 604 negative for tuberculosis. Out of 106 positive cases, 89 (83.96%) were sensitive to Rifampicin and 17 (16.04%) were resistant. Only, 04 (3.77%) were resistant to both Rifampicin and Isoniazid and declared as multidrug-resistant (MDR). It was concluded that children of age 11 to 15 years were more prone to MTB and a minimum percentage of MDR isolates was recorded in age group A (birth to 12 months).

The control of COVID-19 across the world requires the formation of a range of interventions including vaccines to elicit an immune response and immunomodulatory or antiviral therapeutics. Here, we demonstrate the nanoparticle formulation of a highly insoluble drug compound, niclosamide, with known anti SARS-CoV-2 activity as a cheap and scalable long-acting injectable antiviral candidate.

The assumption of interindividual variability being unimodally distributed in nonlinear mixed effects models does not hold when the population under study displays multimodal parameter distributions. Mixture models allow the identification of parameters characteristic to a subpopulation by describing these multimodalities. Visual predictive check (VPC) is a standard simulation based diagnostic tool, but not yet adapted to account for multimodal parameter distributions. Mixture model analysis provides the probability for an individual to belong to a subpopulation (IPmix) and the most likely subpopulation for an individual to belong to (MIXEST). Using simulated data examples, two implementation strategies were followed to split the data into subpopulations for the development of mixture model specific VPCs. The first strategy splits the observed and simulated data according to the MIXEST assignment. A shortcoming of the MIXEST-based allocation strategy was a biased allocation towards the dominating subpopulation. This shortcoming was avoided by splitting observed and simulated data according to the IPmix assignment. For illustration purpose, the approaches were also applied to an irinotecan mixture model demonstrating 36% lower clearance of irinotecan metabolite (SN-38) in individuals with UGT1A1 homo/heterozygote versus wild-type genotype. VPCs with segregated subpopulations were helpful in identifying model misspecifications which were not evident with standard VPCs. The new tool provides an enhanced power of evaluation of mixture models. Electronic supplementary material The online version of this article (10.1007/s10928-019-09632-9) contains supplementary material, which is available to authorized users.

ObjectiveMitotane is used for the treatment of adrenocortical carcinoma. High oral daily doses of typically 1–6 g are required to attain therapeutic concentrations. The drug has a narrow therapeutic index and patient management is difficult because of a high volume of distribution, very long elimination half-life and drug interaction through induction of metabolizing enzymes. The present evaluation aimed at the development of a population pharmacokinetic model of mitotane to facilitate therapeutic drug monitoring (TDM).MethodsAppropriate dosing information, plasma concentrations (1137 data points) and covariates were available from TDM of 76 adrenocortical carcinoma patients treated with mitotane. Using nonlinear mixed-effects modeling, a simple structural model was first developed, with subsequent introduction of metabolic autoinduction. Covariate data were analyzed to improve overall model predictability. Simulations were performed to assess the attainment of therapeutic concentrations with clinical dosing schedules.ResultsA one-compartment pharmacokinetic model with first order absorption was found suitable to describe the data, with an estimated central volume of distribution of 6086 L related to a high interindividual variability of 81.5%. Increase in clearance of mitotane during treatment could be modeled by a linear enzyme autoinduction process. BMI was found to have an influence upon disposition kinetics of mitotane. Model simulations favor a high-dose regimen to rapidly attain therapeutic concentrations, with the first TDM suggested on day 16 of treatment to avoid systemic toxicity.ConclusionThe proposed model describes mitotane pharmacokinetics and can be used to facilitate therapy by predicting plasma concentrations.

Creatinine clearance is an important tool to describe the renal elimination of drugs in pharmacokinetic evaluations and clinical practice. In critically ill patients, unstable kidney function invalidates the steady state assumption underlying equations such as Cockcroft-Gault. While measured creatinine clearance (mCrCL) is often used in non-steady state situations, it assumes that observed data is error-free, neglecting frequently occurring errors in urine collection. In contrast, compartmental non-linear mixed effects models of creatinine allow to describe dynamic changes in kidney function while explicitly accounting for a residual error associated with observations. Based on 530 serum and 373 urine creatinine observations from 138 critically ill patients, a one compartment creatinine model with zero-order creatinine generation rate (CGR) and first-order creatinine clearance (CrCL) was evaluated. An autoregressive approach for inter-occasion variability provided a distinct model improvement compared to a classical approach (ΔAIC -49.0). Fat-free mass (FFM), plasma urea concentration, age and liver transplantation were significantly related to CrCL, while weight and sex were linked to CGR. The model-based CrCL estimates were superior to standard approaches to estimate CrCL (or glomerular filtration rate) including Cockcroft-Gault, mCrCL, four-variable modification of diet in renal disease (MDRD), six-variable MDRD and chronic kidney disease epidemiology collaboration (CKD-EPI) as a covariate to describe cefepime and meropenem pharmacokinetics in terms of objective function value. In conclusion, a dynamic model of creatinine kinetics provides the means to estimate actual CrCL despite dynamic changes in kidney function, and it can easily be incorporated into population pharmacokinetic evaluations.

Background The aim of this study was to identify sources of variability including patient gender and body surface area (BSA) in pharmacokinetic (PK) exposure for high-dose methotrexate (MTX) continuous infusion in a large cohort of patients with hematological and solid malignancies. Methods We conducted a retrospective PK analysis of MTX plasma concentration data from hematological/oncological patients treated at the University Hospital of Cologne between 2005 and 2018. Nonlinear mixed effects modeling was performed. Covariate data on patient demographics and clinical chemistry parameters was incorporated to assess relationships with PK parameters. Simulations were conducted to compare exposure and probability of target attainment (PTA) under BSA adjusted, flat and stratified dosing regimens. Results Plasma concentration over time data (2182 measurements) from therapeutic drug monitoring from 229 patients was available. PK of MTX were best described by a three-compartment model. Values for clearance (CL) of 4.33 [2.95–5.92] L h− 1 and central volume of distribution of 4.29 [1.81–7.33] L were estimated. An inter-occasion variability of 23.1% (coefficient of variation) and an inter-individual variability of 29.7% were associated to CL, which was 16 [7–25] % lower in women. Serum creatinine, patient age, sex and BSA were significantly related to CL of MTX. Simulations suggested that differences in PTA between flat and BSA-based dosing were marginal, with stratified dosing performing best overall. Conclusion A dosing scheme with doses stratified across BSA quartiles is suggested to optimize target exposure attainment. Influence of patient sex on CL of MTX is present but small in magnitude.

The study explores the causal relationship between monetary policy effectiveness and financial inclusion in developed and under-developed countries. Structural Vector Auto-regressive techniques have been inducted to explore the relationship between monetary policy effectiveness and financial inclusion. The study covers the secondary data of 10 developed and 30 underdeveloped countries throughout 2004–2018. It is concluded that monetary policy effectiveness and financial inclusion do not have a contemporaneous impact on each other. Nevertheless, the reduced-form Vector Auto-regressive witness the reverse causality between financial inclusion and monetary policy effectiveness in developed countries. Thus, effective monetary policy enhances financial inclusion in a country, and a higher degree of financial inclusion lowers the inflation rate and makes monetary policy effective. One way causality from monetary policy effectiveness to financial inclusion can be observed in under-developed countries. Using the Structural Vector auto-regressive technique and financial inclusion index composed of three-dimension to examine the relationship of monetary policy effectiveness and financial inclusion in developed and developing countries is considered the study’s significant contribution.

Efforts to build research capacity and capability in low and middle income countries (LMIC) has progressed over the last three decades, yet it confronts many challenges including issues with communicating or even negotiating across different cultures. Implementing global research requires a broader understanding of community engagement and participatory research approaches. There is a considerable amount of guidance available on community engagement in clinical trials, especially for studies for HIV/AIDS, even culturally specific codes for recruiting vulnerable populations such as the San or Maori people. However, the same cannot be said for implementing research in global health. In an effort to build on this work, the Pakistan Institute of Living and Learning and University College London in the UK sought to better understand differences in beliefs, values and norms of local communities in Pakistan. In particular, they have sought to help researchers from high income countries (HIC) understand how their values are perceived and understood by the local indigenous researchers in Pakistan. To achieve this end, a group discussion was organised with indigenous researchers at Pakistan Institute of Living and Learning. The discussion will ultimately help inform the development of a cultural protocol for researchers from HIC engaging with communities in LMIC. This discussion revealed five common themes; (1) religious principles and rules, (2) differing concepts of and moral emphasis on autonomy and privacy, (3) importance of respect and trust; (4) cultural differences (etiquette); (5) custom and tradition (gift giving and hospitality). Based on the above themes, we present a preliminary cultural analysis to raise awareness and to prepare researchers from HIC conducting cross cultural research in Pakistan. This is likely to be particularly relevant in collectivistic cultures where social interconnectedness, family and community is valued above individual autonomy and the self is not considered central to moral thinking. In certain cultures, HIC ideas of individual autonomy, the notion of informed consent may be regarded as a collective family decision. In addition, there may still be acceptance of traditional professional roles such as ‘doctor knows best’, while respect and privacy may have very different meanings.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a global pandemic by the World Health Organisation and urgent treatment and prevention strategies are needed. Many clinical trials have been initiated with existing medications, but assessments of the expected plasma and lung exposures at the selected doses have not featured in the prioritisation process. Although no antiviral data is currently available for the major phenolic circulating metabolite of nitazoxanide (known as tizoxanide), the parent ester drug has been shown to exhibitin vitroactivity against SARS-CoV-2. Nitazoxanide is an anthelmintic drug and its metabolite tizoxanide has been described to have broad antiviral activity against influenza and other coronaviruses. The present study used physiologically-based pharmacokinetic (PBPK) modelling to inform optimal doses of nitazoxanide capable of maintaining plasma and lung tizoxanide exposures above the reported nitazoxanide 90% effective concentration (EC90) against SARS-CoV-2.MethodsA whole-body PBPK model was constructed for oral administration of nitazoxanide and validated against available tizoxanide pharmacokinetic data for healthy individuals receiving single doses between 500 mg – 4000 mg with and without food. Additional validation against multiple-dose pharmacokinetic data when given with food was conducted. The validated model was then used to predict alternative doses expected to maintain tizoxanide plasma and lung concentrations over the reported nitazoxanide EC90in >90% of the simulated population. Optimal design software PopDes was used to estimate an optimal sparse sampling strategy for future clinical trials.ResultsThe PBPK model was validated with AAFE values between 1.01 – 1.58 and a difference less than 2-fold between observed and simulated values for all the reported clinical doses. The model predicted optimal doses of 1200 mg QID, 1600 mg TID, 2900 mg BID in the fasted state and 700 mg QID, 900 mg TID and 1400 mg BID when given with food, to provide tizoxanide plasma and lung concentrations over the reportedin vitroEC90of nitazoxanide against SARS-CoV-2. For BID regimens an optimal sparse sampling strategy of 0.25, 1, 3 and 12h post dose was estimated.ConclusionThe PBPK model predicted that it was possible to achieve plasma and lung tizoxanide concentrations, using proven safe doses of nitazoxanide, that exceed the EC90for SARS-CoV-2. The PBPK model describing tizoxanide plasma pharmacokinetics after oral administration of nitazoxanide was successfully validated against clinical data. This dose prediction assumes that the tizoxanide metabolite has activity against SARS-CoV-2 similar to that reported for nitazoxanide, as has been reported for other viruses. The model and the reported dosing strategies provide a rational basis for the design (optimising plasma and lung exposures) of future clinical trials of nitazoxanide in the treatment or prevention of SARS-CoV-2 infection.

Graphical abstract, The emergence of SARS-CoV-2, and the ensuing global pandemic, has resulted in an unprecedented response to identify therapies that can limit uncontrolled inflammation observed in patients with moderate to severe COVID-19. The immune pathology behind COVID-19 is complex and involves the activation and interaction of multiple systems including, but not limited to, complement, inflammasomes, endothelial as well as innate and adaptive immune cells to bring about a convoluted profile of inflammation, coagulation and tissue damage. To date, therapeutic approaches have focussed on inhibition of coagulation, untargeted immune suppression and/or cytokine-directed blocking agents. Regardless of recently achieved improvements in individual patient outcomes and survival rates, improved and focussed approaches targeting individual systems involved is needed to further improve prognosis and wellbeing. This review summarizes the current understanding of molecular and cellular systems involved in the pathophysiology of COVID-19, and their contribution to pathogen clearance and damage to then discuss possible therapeutic options involving immunomodulatory drug delivery systems as well as summarising the complex interplay between them.

Objectives Internet- and mobile phone-based psychological interventions have the potential to overcome many of the barriers associated with accessing traditional face-to-face therapy. Self-injurious thoughts and behaviors (STB) are prevalent global health problems that may benefit from Internet- and mobile-based interventions. We provide a systematic review and meta-analysis of studies evaluating mobile- and Internet-based interventions for STB, including nonsuicidal self-injury (NSSI). Methods Online databases (PsycINFO, Web of Science, Medline) were searched up to March 2019 for single-arm and controlled trials of Internet- or mobile-based interventions for STB. The potential for bias was assessed using the Cochrane risk of bias tool. Results Twenty-two eligible trials were identified. The research was limited by a lack of controlled designs and small samples. Evidence supports the acceptability of interventions. There is preliminary evidence that these interventions are associated with a decline in STB. A meta-analysis suggested a positive treatment effect on suicidal ideation when compared to treatment as usual, but not when trials with active controls were also considered. Conclusions Overall, Internet- and mobile-based interventions show promise and further controlled trials are warranted, focusing on behavioral outcomes (NSSI, suicidal behavior). This review was preregistered with PROSPERO (CRD42017074065).

Colorectal cancer remains a significant cause of morbidity and mortality worldwide. Half of all patients develop liver metastases, presenting unique challenges for their treatment. The shortcomings of conventional chemotherapy has encouraged the use of nanomedicines; the application of nanotechnology in the diagnosis and treatment of disease. In spite of technological improvements in nanotechnology, the complexity of biological systems hinders the prospect of nanomedicines being applied in cancer therapy at the present time. This review highlights current biological barriers and discusses aspects of tumor biology together with the physicochemical features of the nanocarrier, that need to be considered in order to develop effective nanotherapeutics for colorectal cancer patients with liver metastases. It becomes clear that incorporating an interdisciplinary approach when developing nanomedicines should assure appropriate disease‐driven design and that this will form a critical step in improving their clinical translation. This article is characterized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease, A fundamental understanding of the tumor biology and its physiological features is necessary for the design and development of effective nanomedicines to target cancers.

Biofilm is a complex community of single or different types of microorganisms (bacteria, viruses, fungi, protozoa) attached to a surface and stick to each other through production of extracellular matrix. Salmonella typhi forms biofilm on cholesterol gallstones resulting in carrier state. Once formed, biofilm is difficult to treat. To date cholecystectomy is the only cure for this condition. Manuka honey is known to have tremendous antibiofilm activity against various organisms. S. typhi biofilm was grown in vitro on clinical samples of human cholesterol gallstones by Gallstone tube assay method for 12 days. Biofilm mass was quantified on day 1, 5, 7, 9 and 12 by crystal violet assay and was also examined by scanning electron microscope. Three concentrations w/v of Manuka honey (40%, 60% and 80%) were used, each one at 24, 48 and 72 hours. The most effective concentration (80% w/v) was repeated on two sets of gallstones. Biofilm mass was re quantified by crystal violet assay and was examined by scanning electron microscope. S. typhi formed uniform biofilm on cholesterol gallstone surface. The optical density measurements exhibited a rising pattern with time thereby indicating an increase in biofilm mass. It was 0.2 on day 1 and 0.9 on day 12. With 80% w/v Manuka honey, biofilm mass decreased most effectively with 0.5 OD after 72 hours. Biofilm formation by S, typhi on gallstones is surface specific and bile dependant. Either increasing the duration (beyond 72 hours) of the effective concentration (80% w/v) of honey or increasing the concentration (above 80%) of honey for a specific duration (72 hour) may cause complete disruption of the S. typhi biofilm on gallstone. S. typhi forms biofilm on cholesterol gallstones surface in vitro and it can be visualized by scanning electron microscopy. Biofilm mass can be quantified using crystal violet assay. Among various concentrations 80% Manuka honey for 72 hours is most effective in disrupting S. typhi biofilm on gallstones in vitro as evident from crystal violet assay.

A two way, randomized cross-over bioequivalence study was conducted to analyse the rate and extent of absorption of atorvastatin after a single dose of 80 mg atorvastatin as atorvastatin calcium tablets. The study was carried out using healthy male volunteers (N = 24). A high performance liquid chromatography method was employed to determine the level of drug in human plasma. It was concluded that the test and the reference drug exhibited comparable values of pharmacokinetic parameters. It was also concluded that since there was no significant difference between the rate and extent of absorption of the drug from the test and the reference formulations: these two formulations could thus be declared bioequivalent.

To the best of our knowledge, Non-O1 Vibrio cholerae (NOVC) bacteremia has never been documented in Pakistan. This case report is the first reported case of bacteremia in an infant due to NOVC in Pakistan. A neonate was admitted to a hospital with fever and no history of diarrhea. The isolate was identified biochemically and serologically and was sensitive to all the drugs tested as per CLSI 2014 guidelines.

To compare Bactec MGIT 960 with LJ media in terms of time taken for the initial isolation of mycobacteria.A total of 100 AFB (acid fast bacillus) positive sputum samples were processed and inoculated in both the Lowenstein Jensen (LJ) media and mycobacterium growth indicator tube (MGIT) tubes.Of the 100 samples, positive growth was obtained from all the samples on both the MGIT and LJ media. In MGIT 53% samples grew in 4 days, 30% in 5 days and 17% in 6 days (Mean = 4.6 days) while on LJ media, 44% grew in 30 days, 20% in 35 days and 36% in 44 days (Mean = 37 days). Significant difference was observed between two systems with a p-value of less than 0.05.Bactec MGIT 960 is a much faster and efficient system for the initial isolation of mycobacteria.

Methicillin resistant Staphylococcus aureus (MRSA) continues to be one of the commonest pathogens encountered in clinical as well as laboratory practice. It has become a major health problem worldwide. Newer antimicrobials/agents are urgently needed to combat this problem MRSA resistance to various anti-staphylococcal agents. In the back-drop of this difficult situation Nigella sativa commonly known as black seed (ethanolic extract) was aimed at to evaluate if it had any anti-staphylococcal activity.The extract was prepared by reflux extraction method. Disc diffusion and in agar dilution methods were performed to assess the antibacterial activity. Staphylococcus aureus ATCC 25923 was used as the standard reference strain.All tested strains of MRSA were sensitive to N. sativa extract at a concentration of 4 mg/disc while the extract had an MIC range of 0.2-0.5 mg/ml.The results indicated that N. sativa has inhibitory effect on MRSA. This finding warrants necessity of further investigation of this product of folk medicine.

Diarrhoeal disease is a common cause of major public health concern in many parts of the world including Pakistan.Eighteen stool samples were received from Civil Hospital Mirpur Khas (Sindh). All the specimens were processed for culture and antimicrobial susceptibility according to Clinical Laboratory Standards Institute (CLSI) guidelines.Eight out of eighteen (44.4%) samples were positive for Vibrio cholerae. The isolates were gram negative rods, showed darting motility and were Oxidase positive. Contact with distilled water immobilized all these strains (Mdw). API 20NE was used for the biochemical identification and serological confirmation was done with 'difco' antisera. Kirby-Bauer disc diffusion method was performed for their respective susceptibility to various antibiotics. All these isolates were confirmed to be Vibrio cholerae O1 Biotype El Tor Serotype Ogawa. The isolates were generally sensitive to majority of the antibiotics but resistant to nalidixic acid except one strain. Six out of eight isolates were resistant to co-trimoxazole.Cholera must be suspected in outbreaks of such kind of 'gastro'.

There is a rapidly expanding literature on the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). However, this has not been accompanied by a comprehensive evaluation of the target plasma and lung concentrations of these drugs following approved dosing in humans. Accordingly, concentration 90% (EC90 ) values recalculated from in vitro anti-SARS-CoV-2 activity data was expressed as a ratio to the achievable maximum plasma concentration (Cmax ) at an approved dose in humans (Cmax /EC90 ratio). Only 14 of the 56 analyzed drugs achieved a Cmax /EC90 ratio above 1. A more in-depth assessment demonstrated that only nitazoxanide, nelfinavir, tipranavir (ritonavir-boosted), and sulfadoxine achieved plasma concentrations above their reported anti-SARS-CoV-2 activity across their entire approved dosing interval. An unbound lung to plasma tissue partition coefficient (Kp Ulung ) was also simulated to derive a lung Cmax /half-maximal effective concentration (EC50 ) as a better indicator of potential human efficacy. Hydroxychloroquine, chloroquine, mefloquine, atazanavir (ritonavir-boosted), tipranavir (ritonavir-boosted), ivermectin, azithromycin, and lopinavir (ritonavir-boosted) were all predicted to achieve lung concentrations over 10-fold higher than their reported EC50 . Nitazoxanide and sulfadoxine also exceeded their reported EC50 by 7.8-fold and 1.5-fold in lung, respectively. This analysis may be used to select potential candidates for further clinical testing, while deprioritizing compounds unlikely to attain target concentrations for antiviral activity. Future studies should focus on EC90 values and discuss findings in the context of achievable exposures in humans, especially within target compartments, such as the lungs, in order to maximize the potential for success of proposed human clinical trials.