Trimethoprim bioavailability

The starting dose as well as dose adjustment in therapy are made according to guidelines fixed in the treatment protocols. For pneumocystis carinii pneumonia prophylaxis, trimethoprim-sulfamethoxazole is administered on three consecutive days per week, with the largest possible interval in reference to the weekly methotrexate application. This is done to account for the theoretical enhancement of the antifolic activity of methotrexate by co-administered trimethoprim-sulfamethoxazole (72,73). Because several reports have suggested an improved outcome with bedtime administration, 6-MP is commonly administered in the evening hours (74,75). Also, 6-MP should not be given in combination with milk because the xanthine oxidase (XO) activity contained in milk decreases the bioavailability of 6-MP (76,77,78). 

Potential adverse effects are headache, dizziness, insomnia, fatigue, and gastrointestinal discomfort, although these are typically mild. Lamivudine s bioavailability increases when it is -administered with trimethoprim-sulfamethoxazole. Lamivudine and zalcitabine may inhibit the intracellular phosphorylation of one another therefore, their concurrent use should be avoided if possible. Short-term safety of lamivudine has been demonstrated for both mother and infant. 

Baquiloprim has a high oral bioavailability in animals where it is widely distributed in the body and slowly eliminated (222,223). In cattle, baquiloprim was reported to have a much longer half-life and a larger volume of distribution than trimethoprim (223). Both urine and bile are important routes of elimination. 

TRIMETHOPRIM GANCICLOVIR/ VALGANCICLOVIR Possibly t adverse effects (e.g, myelosuppression) when trimethoprim is co administered with ganciclovir or valgancidovir Small t in bioavailability possible additive toxicity Well tolerated in a study. For patients at risk of additive toxicities, use only if benefits outweigh risks, and monitor FBC closely... 

Table 2.2 Oral bioavailability in horses of rifampin (5mg/kg aqueous suspension), metronidazole (20mg/kg aqueous suspension), pyrimethamine (1 mg/kg suspended in corn syrup), trimethoprim (5mg/kg) and sulphadiazine (25mg/kg oral paste combination preparation).

Following oral administration, lamivudine is absorbed rapidly with a bioavailability of about 80% in adults. Peak plasma levels average approximately 1000 ng/mL after 100-mg doses. Lamivudine is distributed widely in a volume comparable with total-body water. The plasma t,/2 of elimination averages about 9 hours, and approximately 70% of the dose is excreted unchanged in the urine. About 1% is metabolized to an inactive trawY-sulfoxide metabolite. In HBV-infected children, doses of 3 mg/kg per day provide plasma exposure and trough plasma levels comparable with those in adults receiving 100 mg daily. Dose reductions are indicated for moderate renal insufficiency (creatinine clearance <50 ml/min). Trimethoprim decreases the renal clearance of lamivudine. 

Both age and diet may influence sulfonamide absorption in calves. Oral absorption of sulfadiazine was very slow in calves on milk diets, and bioavailability was greater in ruminating than milk-fed pre-ruminant calves. Trimethoprim, on the other hand, was well absorbed in preruminant calves but not in ruminating animals, possibly as a result of inactivation by ruminal microflora. 

Langlois Y etal. (1972). A bioavailability study on three oral preparations of the combination trimethoprim-sulfamethoxazole. / Clin Pharmacol New Drugs 12 19 200. 

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