No abstract

Recent clinical research has shown that atorvastatin (ATO) in combination with cholesterol absorption inhibitor ezetimibe (EZE) significantly reduces LDL-C level in patients with hypercholesterolemia, showing a superior lipid-lowering efficacy compared to statin alone. With no information currently available on the interaction between the two drugs, a pharmacokinetic study was conducted to investigate the influence of EZE on ATO and conversely when the two drugs were coadministered. The purpose of this study was to investigate the presence of differences in the pharmacokinetic profiles of capsules containing ATO 80 mg, EZE 10 mg or the combination of both 80/10 mg administered to healthy Mexican volunteers. This was a randomized, three-period, six-sequences crossover study. 36 eligible subjects aged between 20 to 50 years were included. Blood samples were collected up to 96 h after dosing, and pharmacokinetic parameters were obtained by non-compartmental analysis. Adverse events were evaluated based on subject interviews and physical examinations. Area under the concentration-time curve (AUC) and maximum plasma drug concentration (Cmax) were measured for each drug alone or together and tested for bioequivalence-based hypothesis. The estimation computed (90% confidence intervals) for AUC and Cmax, were 96.04% (85.88–107.42%) and 97.04% (82.36–114.35%), respectively for ATO–EZE combination versus ATO alone, while 84.42% (77.19–92.32%) and 95.60% (82.43–110.88%), respectively, for ATO–EZE combination versus EZE alone were estimated. These results suggest that ATO and EZE have no relevant pharmacokinetic drug–drug interaction.

Several clinical trials have substantiated the efficacy of the co-administration of statins like atorvastatin (ATO) and fibrates. Without information currently available about the interaction between the two drugs, a pharmacokinetic study was conducted to investigate the effect when both drugs were co-administered. The purpose of this study was to investigate the pharmacokinetic profile of tablets containing ATO 20 mg, or the combination of ATO 20 mg with fenofibrate (FNO) 160 mg administered to healthy Mexican volunteers. This was a randomized, two-period, two-sequence, crossover study; 36 eligible subjects aged between 20–50 years were included. Blood samples were collected up to 96 h after dosing, and pharmacokinetic parameters were obtained by non-compartmental analysis. Adverse events were evaluated based on subject interviews and physical examinations. Area under the concentration-time curve (AUC) and maximum plasma drug concentration (Cmax) were measured for ATO as the reference and ATO and FNO as the test product for bioequivalence design. The estimation computed (90% confidence intervals) for ATO and FNO combination versus ATO for Cmax, AUC0-t and AUC0-∞, were 102,09, 125,95, and 120,97%, respectively. These results suggest that ATO and FNO have no relevant clinical-pharmacokinetic drug interaction.

A high-throughput ultra-performance liquid chromatography coupled to tandem mass spectrometry (LC-ESI-MS-MS) method was developed for the determination of pinaverium bromide in human plasma. Protein precipitation with acetonitrile was used to extract pinaverium and itraconazole (as internal standard) from 500 µL plasma samples. The chromatographic separation was achieved with an Acquity UPLC BEH C18 column (1.7 µm, 2.1 × 100 mm) using a mixture of acetonitrile-5 mM ammonium formate (80:20, v/v) as mobile phase. Isocratic elution at 0.3 mL/min was used. Detection was performed by positive ion electrospray tandem mass spectrometry on a XEVO TQ-S by multiple reaction monitoring mode. The mass transitions monitorized were as follows: m/z 511.2 → 230 for pinaverium bromide, and m/z 705.29 → 392.18 for the itraconazole. The method was validated over a concentration range of 12-12,000 pg/mL. The chromatographic method runtime is 2.5 min and was applied to characterize the pharmacokinetics of pinaverium bromide after the oral administration of 100 mg to healthy Mexican subjects.

Introduction. Oral ciprofloxacin extended-release formulation decreases the risk of treatment failure and prevents the development of antimicrobial resistance. However, non-equivalent formulations lead to subtherapeutic plasma drug concentrations, increasing the risk of such problems. Objective. To determine the bioequivalence of two oral ciprofloxacin extended-release tablet formulations (1,000 mg) in healthy Mexican volunteers. Material and Methods. In this open-label 2 × 2 crossover design study, 26 healthy volunteers were randomly allocated to receive a single dose of the reference drug Cipro XR® (Bayer, Mexico) and the test formulation Ciproflox DM® (Senosiain Laboratories, Mexico). Blood samples were obtained for 24 hours. Ciprofloxacin plasma levels were quantified using a validated liquid chromatography method. Pharmacokinetic parameters were obtained by standard non-compartmental analysis. In order to determine bioequivalence, log-transformed test/reference ratios of Cmax, AUC0-t, and AUC0-inf were compared by an analysis of variance, followed by the 90 % confidence intervals and the Schuirmann bilateral test. Results. The 90 % confidence intervals ranged from 85.69 to 114.31 % for Cmax, 85.16-115.84 % in AUC0-t, and 85.39-114.61 % for AUC0-inf, all cases were within bioequivalence acceptance criteria (80-125 %). Schuirmann test verified the probability that the values were within these criteria (p < 0.05). No side-effects were observed with any treatment. Conclusions. The results obtained demonstrate bioequivalence between the analyzed formulations.