G6PD deficiency alleles in a malaria-endemic region in the Western Brazilian Amazon.

Background: Plasmodium vivax parasites are the predominant cause of malaria infections in the Brazilian Amazon. Infected individuals are treated with primaquine, which can induce haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals and may lead to severe and fatal complications. This X-linked disorder is distributed globally and is caused by allelic variants with a geographical distribution that closely reflects populations exposed historically to endemic malaria.

Maximal inhibition of intestinal first-pass metabolism as a pragmatic indicator of intestinal contribution to the drug-drug interactions for CYP3A4 cleared drugs.

For certain CYP3A4 substrates intestinal first-pass metabolism makes a substantial contribution to low oral bioavailability and extent of drug-drug interactions (DDI). In order to include the contribution of enzyme inhibition in the gut wall in the assessment of DDI potential, the ratio of the intestinal wall availability in the presence and absence of an inhibitor (F(G)(') and F(G), respectively) has been incorporated into a prediction equation based on hepatic enzyme interactions. This approach has been applied for both reversible and irreversible DDIs, involving 36 different inhibitors and 11 CYP3A4 substrates.

Multiple inhibition mechanisms and prediction of drug-drug interactions: status of metabolism and transporter models as exemplified by gemfibrozil-drug interactions.

Purpose: To assess the consequences of multiple inhibitors and differential inhibition mechanisms on the prediction of 12 gemfibrozil drug-drug interactions (DDIs). In addition, qualitative zoning of transporter-related gemfibrozil and cyclosporine DDIs was investigated.

Methods: The effect of gemfibrozil and its acyl-glucuronide on different enzymes was incorporated into a metabolic prediction model.

Spontaneous gastroduodenal perforation in 16 dogs and seven cats (1982-1999).

The records of 23 dogs and cats diagnosed with spontaneous gastroduodenal perforation (GDP) were retrospectively reviewed. Survival was 63% in dogs and 14% in cats. Rottweilers <5 years of age were overrepresented.