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Purpose: To develop a simple, novel, sensitive and rapid reverse phase high performance liquid chromatographic method for simultaneous determination of paclitaxel, sorafenib and omeprazole in standard solutions and spiked human plasma and its application to the in-vitro and in-vivo evaluation of paclitaxel polymeric nanoparticle formulations. Methods: The method was tested for the assessment of paclitaxel, omeprazole and sorafenib using tamoxifen citrate as internal standard. The analysis was performed at a wavelength of 235 nm using Thermo HS C18 column, 40 °C column oven temperature, acetonitrile and water (70:30 v/v, pH 3.37 adjusted with phosphoric acid) as a mobile phase and at a flow rate of 0.8 ml/min. All analytes were extracted by simple protein precipitation method using acetonitrile. The linearity was assessed in the concentration range of 1 - 2000 ng/mL for paclitaxel, omeprazole and sorafenib. Results: The developed chromatographic method effectively separated omeprazole, paclitaxel, sorafenib and IS with retention time of 3.93, 5.18, 6.43 and 9.93 min, respectively. The chromatograms of the three target compounds and IS showed good resolution and peak separation. The LOD of the method was 1, 5 and. 5 ng/mL while the LOQ was 2, 7.5 and 10 ng/mL, for paclitaxel, sorafenib and omeprazole, respectively. Conclusion: The proposed RP-HPLC–UV method for the assessment of paclitaxel, sorafenib and omeprazole in standard solutions and spiked plasma is simple, economical, sensitive and robust. The method is also suitable for the analysis of paclitaxel in nanoformulations and for its pharmacokinetic studies in an animal model. [ABSTRACT FROM AUTHOR]

In current study, the pharmacokinetics (PK) of rosuvastatin were evaluated in Pakistani healthy volunteers and compared with those reported in other population. This was a randomized and open labeled clinical trial in which a single oral dose of 40 mg rosuvastatin was administered to the overnight fasted healthy volunteers. Plasma concentrations of rosuvastatin were quantified by a validated liquid chromatography-tandem mass spectrometry method. The PK parameters of rosuvastatin and its metabolite N-desmethyl-rosuvastatin were determined by PK specific software i.e., PK-Summit® (PK-Solutions). A total of 20 healthy volunteers having BMI in the normal ranges were included in this study. All PK parameters were represented as mean ± SD and 95% confidence intervals of the means have been calculated. The Cmax (29.07 ± 6.88 ng/mL), [AUC]0∞(206.65 ± 55.27 ng/hr/mL) and CL/F (3275.26 ± 1072.87 mL/hr) were slightly higher in our study, whereas the values of Vd (19377.23 ± 9114.29 mL) and tmax (3.0 ± 0.46 hr) were comparatively smaller. Overall, the PK parameters of rosuvastatin determined in our study were in compliance with other reported. Therefore, no adjustments in the dosing schedule or dose are warranted. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of hashish consumption on liver function and coagulation parameters. Methodology: Chronic hashish consumers (n=62) and healthy controls (n=43) were studied. Serum bilirubin, Liver enzymes alanine transaminase and alkaline phosphatase were studied to evaluate hepatic malfunctioning using manual colorimetric method. The coagulation parameters prothrombin time and activated partial thromboplastin time were studied to evaluate the risks of bleeding disorders using manual-tilt method. Results: An increase in the blood levels of total bilirubin (P= 0.014), alanine transaminase (P= 0.024) and alkaline phosphatase (P= 0.025) was observed in chronic hashish consumers as compared to the non-hashish using group. A significant prolongation in prothrombin time (P= 0.026) and activated partial thromboplastin time (P= 0.029) was found in chronic hashish consumers as compared to the control group. Conclusion: An increase in the levels of liver enzymes and coagulation parameters were observed in hashish users as compared to the control group which indicates that hashish consumption affect the liver functions. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate a comparative single dose (40mg) pharmacokinetics (PK) of Omeprazole (OMP) and its two metabolites, 5-hydroxy Omeprazole (5-OH-OMP) and Omeprazole sulphone (OMP-S) in poor (PM) and extensive (EM) metabolizer Pakistani healthy adult volunteers. The frequency of CYP2C19 and CYP3A4 varies widely in different populations. The present study was conducted to evaluate the PK of OMP and its two metabolites in Pakistani population and to review different studies conducted after administration of single dose of OMP. Twenty two subjects were enrolled in this study and divided into two groups. The CYP2C19 phenotyping was evaluated by the metabolic ratio of OMP to 5-OH-OMP. It was a single dose, open label study and the blood samples from subjects were collected at different time intervals until 24 hours. The PK parameters were calculated using the PK-summit software. The metabolic ratio of area under the plasma concentration-time curve AUCOMP/5-OH-OMP was 1.86 ± 0.572 and13.84 ± 2.504 for EM and PM, respectively; maximum plasma concentration (Cmax) of OMP was increased by two folds for PM while the AUC∞ was increased by 3 folds; the Cmax and AUC∞ of 5-OH-OMP decreased for PM by 2 folds while there was 3 fold increase observed in the Cmax and AUC∞ of OMP-S. The PK of OMP and its metabolites in different populations were also discussed, and issues regarding CYP2C19 and CYP3A4 genotyping were also extensively reviewed. In EM of CYP2C19 the concentration of 5-OH-OMP is higher while that of OMP-S is lower. This study as well as reported studies reveals that in PM of CYP2C19 more drugs are available for CYP3A4 to be metabolized. A correlation between CYP2C19 EM and PM activity with CYP3A4 needs to be established. [ABSTRACT FROM AUTHOR]

We compared the plasma antioxidants level of normal control group with that of hypertensive patients in order to test the hypothesis "that antioxidants level has been diminished in hypertensive patients and that antioxidants are interconnected with each other making a network. The plasma and red blood cells antioxidants level of newly diagnosed hypertensive patients [(n=30), (mean age 53 years), (mean systolic BP 158 mmHg, mean diastolic BP 100 mmHg)] were compared to those of the control subjects [(n=30), (mean age 50 years), (mean systolic BP 126 mmHg, mean diastolic BP 90 mmHg)] using liquid chromatography linked with electrochemical detector (HPLC-ECD). The data was analyzed by Minitab software at a 95% confidence interval (pR0.05) as significant. The comparison between the two groups was made applying 2-sample and paired t-test. The individual concentration of antioxidants in both plasma and red blood cells of hypertensive patients was lower in comparison with that of control group while the oxidized/reduced ratios of these antioxidants were higher in hypertensive patients in comparison with that of control group. It is concluded that antioxidants level had been diminished in the hypertensive patients when compared with control group. The overall concentration of all antioxidants has been diminished in the oxidative stress induced pathological conditions which confirm that the studied antioxidants are working in a network. This study may be helpful for the recommendation of antioxidants intervention. [ABSTRACT FROM AUTHOR]

Over the past few years, taxanes have emerged as a new class of anticancer drugs. Docetaxel (DTX) the prototype of this class has been approved for the treatment of broad range of cancers. However, to date the commercial preparation of DTX (Taxotere®) is accompanying adverse side effects, intolerance, and poor solubility, which can be overcome by encapsulating them using solid lipid nanoparticles (SLNs). SLNs represent versatile delivery system of drugs with newer forms such as polymer-solid lipid hybrid, surface modified and long circulating nanoparticles bringing forth improved prospects for cancer chemotherapy. In this review, the authors have discussed the current uses of various SLNs formulations of DTX with key emphasis on controlled and site-specific drug delivery along with enhanced antitumour activity elucidated via in vitro and in vivo studies. Furthermore, the review article highlights few approaches that can be used in combination with existing DTX-loaded SLNs to supplement DTX drug delivery. [ABSTRACT FROM AUTHOR]