BACKGROUND: Tablet splitting is a well-established medical practice in clinical settings for multiple reasons, including cost savings and ease of swallowing. However, it does not necessarily result in weight-uniform half tablets.
This assay method was valid within a wide range of plasma concentrations and may be proposed as a suitable method for pharmacokinetic studies, therapeutic drug monitoring implementation, and routine clinical applications, especially for some populations of patients who receive a combination of these drugs.
A simple validated high-performance liquid chromatography (HPLC) assay was developed for determination of diflunisal and naproxen in human plasma samples. This is to compare the bioavailability of diflunisal-naproxen fixed-dose combination (FDC) with their separate dosage forms. The in vitro dissolution study was adopted to compare the dissolution behavior of FDC with respect to separate marketed tablets. In vivo study was conducted according to a single-center, randomized, single-dose, laboratory-blinded, 2 Way, Cross-Over Study with a washout period of 10 days. Under fasting conditions, 24 healthy Egyptian male volunteers were randomly allocated to receive a single oral dose of either one FDC tablet or co-administration of two separate diflunisal and naproxen marketed tablets. Plasma samples were obtained over a 72-h interval and analyzed for diflunisal and naproxen by reversed phase liquid chromatography with UV detection. The pharmacokinetic parameters Cmax, AUC0-t, AUC0-∞, tmax, and t1/2 were determined from plasma concentration-time profiles. The 90% confidence intervals for the ratio of log transformed values of Cmax, AUC0-t, and AUCt-∞ of the 2 treatments were within the acceptable range (0.8-1.25) for bioequivalence. From pharmacokinetic and in vitro studies perspectives, 1 FDC tablet demonstrated similar relative bioavailability with the 2 individual -reference tablets.
Domperidone is a dopamine antagonist with a unique gastroprokinetic and antiemetic properties. This study was conducted to evaluate the pharmacokinetics (PKs) and comparative bioavailability of suspension (reference) and tablet (test) formulations of domperidone. In vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, two way, cross-over study with a washout period of 1 week. Under fasting conditions, 26 healthy Egyptian male volunteers were randomly allocated to receive a single oral dose of either 20 mL domperidone or two tablets (each contains 10 mg domperidone) of marketed suspension and tablet formulations. Plasma samples were obtained over a 24-hour interval and analyzed for domperidone by reversed phase liquid chromatography with fluorescence detection. The 90% confidence intervals for the ratio of log transformed values of Cmax , AUC0-t , and AUCt-∞ of the two treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, in this small study in healthy Egyptian adult male volunteers, a single 20 mg dose of the tablet formulation was bioequivalent to a single 20 mg dose of the suspension formulation based on the US FDA's regulatory definition. No adverse events occurred or were reported during the study and both formulations were well tolerated.
The developed analytical method was suitable for use in pharmacokinetic studies and therapeutic drug monitoring implementation. Sulpiride was well tolerated by the patients without any serious adverse events being observed. The double peaks in the serum concentration-time profiles could be due to differential rates of absorption along the gastrointestinal tract. The discontinuous absorption model with two sites of absorption was adequate to describe the double-peak of the sulpiride plasma profile. ClinicalTrials. gov identifiers: NCT01777685.
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