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Aim Methods Results Conclusion Clinical Trial Registration Number Brensocatib is an oral, selective, competitive and reversible dipeptidyl peptidase 1 inhibitor in development for the treatment of bronchiectasis. This study evaluated the pharmacokinetics (PKs), safety and tolerability of brensocatib in participants with varying degrees of renal impairment and normal renal function.In this phase 1, multicentre, open‐label study, 28 participants with mild, moderate or severe renal impairment (estimated glomerular filtration rate [eGFR] 60 to <90, 30 to <60 and 15 to <30 mL/min/1.73 m2, respectively) or normal renal function (≥90 mL/min/1.73 m2) received a single oral 25‐mg dose of brensocatib. Blood samples were collected to measure brensocatib PKs at predetermined time points over the 14‐day study period. PK parameters were derived using noncompartmental methods.Demographic and baseline characteristics were similar across groups. There were no significant differences between groups in brensocatib PK parameters. The mean coefficient of variation (CV) of elimination half‐life of brensocatib was 37.0 (15.3), 42.8 (21.7), 36.3 (22.9) and 39.1 (17.8) h for mild, moderate, severe and normal renal function groups, respectively. Single‐dose brensocatib was quickly absorbed; all groups had a median time to maximum observed plasma concentration of 1 h. Regression model analyses indicated no significant relationships between selected brensocatib PK parameters and eGFR. No treatment‐emergent adverse events were reported during the study.Single‐dose brensocatib was well tolerated. The study data do not indicate a significant effect of renal impairment on brensocatib elimination and systemic exposure, suggesting that dose adjustment of brensocatib is not necessary in participants with renal impairment.NCT05673603. [ABSTRACT FROM AUTHOR]

A pilot study of 20 males was conducted with a sample of healthy males selected for normal characteristics. Each was administered an 8-week trial of a supplement using natural nutrients [...]

Several factors appear to contribute to errors in prescribing medication for hospitalized patients. Physicians and pharmacists analyzed significant prescription errors caught and corrected by pharmacists at a large teaching hospital. They found 2,103 errors in a year period for a rate of 4 per 1,000 medication orders. Factors included failing to take declining kidney or liver function into account; ignoring patient history of allergy; using the wrong name, dosage form, or abbreviation; calculating errors; and overdosing. Many of these errors could be eliminated through such strategies as education, computer programs, and dosage standardization., Objective.--To quantify the type and frequency of identifiable factors associated with medication prescribing errors. Design and Setting.--Systematic evaluation of every third prescribing error detected and averted by pharmacists in a 631-bed tertiary care teaching hospital between July 1, 1994, and June 30, 1995. Each error was concurrently evaluated for the potential to result in adverse patient consequences. Each error was retrospectively evaluated by a physician and 2 pharmacists and a factor likely related to the error was identified. Participants.--All physicians prescribing medications during the study period and all staff pharmacists involved in the routine review of medication orders. Main Outcome Measures.--Frequency of association of factors likely related to medication errors in general and specific to medication classes and prescribing services (needed for medical, pediatric, obstetric-gynecologic, surgical, or emergency department patients); and potential consequences of errors for negative patient outcomes. Results.--A total of 2103 errors thought to have potential clinical importance were detected during the 1-year study period. The overall rate of errors was 3.99 errors per 1000 medication orders, and the error rate varied among medication classes and prescribing services. A total of 696 errors met study criteria (ie, errors with the potential for adverse patient effects) and were evaluated for a likely related factor. The most common specific factors associated with errors were decline in renal or hepatic function requiring alteration of drug therapy (97 errors, 13.9%), patient history of allergy to the same medication class (84 errors, 12.1%), using the wrong drug name, dosage form, or abbreviation (total of 79 errors, 11.4%, for both brand name and generic name orders), incorrect dosage calculations (77 errors, 11.1%), and atypical or unusual and critical dosage frequency considerations (75 errors, 10.8%). The most common groups of factors associated with errors were those related to knowledge and the application of knowledge regarding drug therapy (209 errors, 30%); knowledge and use of knowledge regarding patient factors that affect drug therapy (203 errors, 29.2%); use of calculations, decimal points, or unit and rate expression factors (122 errors, 17.5%); and nomenclature factors (incorrect drug name, dosage form, or abbreviation) (93 errors, 13.4%). Conclusions.---Several easily identified factors are associated with a large proportion of medication prescribing errors. By improving the focus of organizational, technological, and risk management educational and training efforts using the factors commonly associated with prescribing errors, risk to patients from adverse drug events should be reduced. JAMA. 1997;277:312-317

Combination drug therapy with zidovudine plus didanosine or zalcitabine does not appear to prolong life in AIDS patients. This was demonstrated in a study of 1,102 AIDS patients who took zidovudine alone, zidovudine and didanosine or zidovudine and zalcitabine. After an average follow-up of three years, death rates were similar in the three groups. Those taking combination therapy also experienced more side effects. It is possible that combination therapy could benefit AIDS patients who have not taken zidovudine for long periods of time.

Zidovudine treatment of HIV-infected adults in the early stages of infection may not extend survival with or without AIDS. HIV-infected individuals without symptoms and with a CD4 cell count of at least 500 cells/cubic milliliter were divided into three groups: 547 who initially received a placebo, 549 who received 500 milligrams/day of zidovudine, and 541 who received 1500 mg/day of zidovudine. After two years all participants were given the option of receiving 500 mg/day of zidovudine. Patients were followed for a median of 5 years. There were no significant differences between the groups in survival without AIDS. The death rate in each group was approximately 2 years/100 person-years of follow-up. However, the median amount of time for CD4 counts to drop below 500 cells/cubic ml was 1.0 in the delayed treatment group and 1.5 in the immediate treatment groups. Thus, early treatment did delay CD4 depletion. The overall frequency of side effects was low, but most significant in the 1500 mg/day group.

Zidovudine appears to retard the development of AIDS in those infected with HIV, but its effectiveness seemingly lasts no longer than approximately two years. A total of 1,565 HIV-positive patients who were asymptomatic for AIDS but had CD4 lymphocyte counts below 500 per microliter were given either zidovudine or a placebo and were followed for up to 4.5 years. A dose of 500 milligrams of zidovudine was found to significantly slow the progression to AIDS. However, its effectiveness was less pronounced on those whose initial CD4 cell counts were less than 300 per microliter, and the relative risk of AIDS progression between those receiving zidovudine and those receiving a placebo was the same after roughly 2 years. Other drug treatment and prevention measures should be developed to overcome the long-term ineffectiveness of zidovudine., Objective.--To determine the durability of zidovudine-induced delay in clinical progression of asymptomatic human immunodeficiency virus (HIV) disease and to assess the relationship between this effect and the entry [CD4.sup.+] cell count. Design and Interventions.--Extended follow-up data from subjects participating in protocol 01 9 of the AIDS [acquired immunodeficiency syndrome] Clinical Trials Group were examined. Subjects were offered a total daily dose of 500 mg of open-label zidovudine after the unblinding of the original randomized trial in 1989. Original treatment groups included placebo, 500 mg of zidovudine, or 1500 mg of zidovudine daily in divided doses. Three distinct analyses were conducted to assess the duration of zidovudine&apos;s effect on progression to AIDS or death: (1) analysis of all follow-up information from all subjects, (2) analysis of all subjects but with follow-up of original placebo-assigned subjects censored at the time open-label zidovudine was initiated, and (3) analysis of the effect of initiating zidovudine in subjects initially assigned to receive placebo. Setting.--University-based and university-affiliated AIDS research clinics participating in AIDS Clinical Trials Group protocol 019. Patients.--A total of 1565 asymptomatic HIV-infected subjects with entry [CD4.sup.+] cell counts less than 0.50x[10.sup.9]/L (500/[mu]L). Main Outcome Measure.--Time to progression to AIDS or death. Results.--During follow-up of up to 4.5 years (mean, 2.6 years), 232 subjects progressed to AIDS or died. In each of the three analyses described herein, zidovudine was associated with a significant (P=.008,.004,.007) decrease in the risk of such progression. However, each of these analyses also indicated a decreasing placebo:zidovudine relative risk with duration of use (P=.002,.08,.04), suggesting a nonpermanent effect. The duration of benefit appeared to be related to entry [CD4.sup.+] cell count, with greater benefit in those with higher counts at entry. No significant differences in survival were found between those originally randomized to zidovudine or placebo. Conclusions.--Zidovudine at 500 mg/d caused a significant delay in progression to AIDS or death, but its earlier use in asymptomatic disease was not associated with an additional prolongation of survival compared with delayed initiation. The delay in progression diminished over time especially in subjects with entry [CD4.sup.+] cell counts less than 0.30x[10.sup.9]/L (300/[mu]L). Treatment strategies that alter drug regimens before the loss of zidovudine benefit should be explored. (JAMA. 1994;272:437-442)

It has recently been shown that zidovudine (formerly called AZT) provides benefits to people with early human immunodeficiency virus (HIV) disease and who are either without symptoms or have only mild symptoms. Although the rates of newly acquired HIV infections appear to have stabilized for American homosexuals, they have continued to increase in American blacks, Hispanics, women, and intravenous (IV) drug users. A study was undertaken to determine if the previously noted benefits of zidovudine treatment also apply to blacks, Hispanics, women, and IV drug users. There were 2,048 patients with early HIV infection who were analyzed; among these subjects, there were 155 blacks, 190 Hispanics, 144 women, and 221 IV drug users. The rate of progression of HIV disease to acquired immune deficiency syndrome (AIDS) was significantly lower among those given zidovudine therapy than those given placebo among the blacks, whites, Hispanics, non-Hispanics, men, and non-IV drug abusers. For women and IV drug users, there was no statistically significant difference in disease progression between the two treatment groups. The relative risks for women and IV drug users were similar to those for men and non-IV drug abusers. It is concluded that the beneficial effect of zidovudine in delaying the progression of HIV infection to AIDS, as established in larger studies, also applies to minority subpopulations. (Consumer Summary produced by Reliance Medical Information, Inc.)

1. Absorption, distribution, metabolism, transport and elimination properties of omadacycline, an aminomethylcycline antibiotic, were investigatedin vitroand in a study in healthy male subjects. 2. Omadacycline was metabolically stable in human liver microsomes and hepatocytes and did not inhibit or induce any of the nine cytochrome P450 or five transporters tested. Omadacycline was a substrate of P-glycoprotein, but not of the other transporters. 3. Omadacycline metabolic stability was confirmed in six healthy male subjects who received a single 300 mg oral dose of [14C]-omadacycline (36.6 μCi). Absorption was rapid with peak radioactivity (∼610 ngEq/mL) between 1–4 h in plasma or blood. The AUClastof plasma radioactivity (only quantifiable to 8 h due to low radioactivity) was 3096 ngEq h/mL and apparent terminal half-life was 11.1 h. Unchanged omadacycline reached peak plasma concentrations (∼563 ng/mL) between 1–4 h. Apparent plasma half-life was 17.6 h with biphasic elimination. Plasma exposure (AUCinf) averaged 9418 ng h/mL, with high clearance (CL/F, 32.8 L/h) and volume of distribution (Vz/F 828 L). No plasma metabolites were observed. 4. Radioactivity recovery of the administered dose in excreta was complete (>95%); renal and fecal elimination were 14.4% and 81.1%, respectively. No metabolites were observed in urine or feces, only the omadacycline C4-epimer. [ABSTRACT FROM PUBLISHER]