Proton pump inhibitors. Compliance with a mandated step-up program.

OBJECTIVE: To assess compliance with a step-up approach to proton pump inhibitor (PPI) therapy before implementation of a new provincial policy to promote histamine-type 2 receptor antagonist (H2RA) use before PPI therapy. DESIGN: Population-based, retrospective, open cohort study using prescribing and medical procedure data from January 1, 1995, to April 30, 1999. SETTING: Health administration databases for the universal health care system in Ontario. PARTICIPANTS: Approximately 1.4 million residents of Ontario older than 65 years. MAIN OUTCOME MEASURES: Proportion of patients who received a trial of H2RA therapy or gastrointestinal diagnostic testing 12 months before starting PPI therapy in 1996. RESULTS: Among the 25,870 patients who met study criteria in 1996, about 63% had received H2RAs 12 months before starting PPI therapy and 73% had had a trial of H2RAs or gastrointestinal diagnostic testing. Repeat analysis for January through April 1999, following the new policy implementation, showed that about 72% of patients had had a trial of H2RAs within 12 months of starting PPI therapy. CONCLUSION: A modest gain (9%) in compliance with using H2RA therapy within 12 months before starting PPI therapy was seen following introduction of the step-up intervention. In future, costs and benefits of potential interventions should be carefully considered before implementing new policies.

Determination of clonixin in plasma and urine by reversed-phase high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method that enables the determination of clonixin in human plasma and urine samples is described. Recovery of the drug was over 87.6 and 80.7% for plasma and urine, respectively. The limit of quantitation of the method was established as 10 ng/ml in plasma and 20 ng/ml in urine samples, with RSDs of less than 11.1%. The applicability of the method was further assessed by determining the plasma concentrations time course of clonixin in six healthy volunteers after single oral dose administration of 150 and 300 mg of clonixin and Clonix.

Dissolution of omeprazole from delayed-release solid oral dosage forms.

The evaluation of the biopharmaceutical quality of omeprazole enteric-coated products (granules in capsules) with respect to its dissolution characteristics is not specifically regulated in any of the most common official pharmacopoeia. USP 23 includes a general monograph for enteric-coated products. This paper reports the evaluation of the medium pH effect on the dissolution rates of omeprazole from four omeprazole-containing products of different manufacturers. It is concluded that the USP 23 recommended dissolution procedure for enteric-coated products is not suitable due to the degradation of omeprazole under such conditions. Furthermore, the medium with pH 8.0 showed different dissolution rates not observed at pH 7.4, allowing discrimination between products of different manufacturers.

Improved bioavailability of a micronized megestrol acetate tablet formulation in humans.

Megestrol acetate, a progestogen widely used in the palliative treatment of endometrial carcinoma and breast cancer, is currently administered orally as a solid dosage form. Bioavailability of the drug following oral administration is closely related to the effectiveness and safety profile of the drug in formulation. Improved immediate-release formulations should allow improved drug delivery into the systemic circulation and, at the end, to the site of action. The micronization of drugs is one of the technological procedures to achieve such a purpose. This paper reports the design and results obtained in an in vivo study of the bioavailability of a micronized megestrol acetate tablet formulation compared to a conventional form. A significant increase in the drug bioavailability was observed, in either the rate or the extent of absorption. In vitro dissolution data of the two study formulations reflected the in vivo findings.

Bioequivalence evaluation of two omeprazole enteric-coated formulations in humans.

Omeprazole, a proton pump inhibitor, effectively suppresses the gastric acid secretion in the parietal cells of the stomach. Several previously published papers focus on the pharmacokinetics of the drug and its interactions with physiological aspects or with other drugs. The increasing number of omeprazole containing products available in the market, raises questions of therapeutic equivalence and/or generic substitution. The bioequivalence evaluation between two or more formulations provides information about in vivo performance. In a favorable decision regarding bioequivalence, the products are considered to have a similar therapeutic efficacy when used under the same therapeutic conditions. This paper reports the design, results and some important aspects involved in a bioequivalence study between two solid oral formulations from different manufacturers. Some important findings were the high intra-subject variability observed for Cmax and the variability observed between subject profiles, probably caused by the multi-unit type of formulations studied.