Fluorometric and Microbiological Assays for Rifampicin and the Determination of Serum Levels in the Dog

Abstract

Rifampicin is oxidized with hydrogen peroxide to a product that is fluorescent in alkaline solutions. Maximum fluorescence is measured at 480 nm with an excitation wavelength of 370 nm. The lower limit of detection of rifampicin in water is 0.1 μg/ml. A microbiological assay with Staphylococcus aureus 560 as the assay organism verified the reliability of the fluorometric assay. The fluorametric and microbiological assays were applied to the estimation of rifampicin in serum and were used to obtain concentration-time data for dogs that had been treated orally with 10 mg/kg rifampicin. Half-life of rifampicin in the dog was 8 h.

Treatment of canine leproid granuloma syndrome: preliminary findings in seven dogs

“…24 Unpublished clinical trials suggest that rifampicin may induce serious side-effects more frequently in dogs: increases in liver enzyme activities developed in as many as 20% of dogs receiving 5 to 10 mg/kg of rifampicin daily and these biochemical alterations may progress to clinical hepatitis. 25 Mild increases in ALP may be benign, although a substantially increased ALT signals the need to discontinue therapy. Some authors recommend that the dosage of rifampicin given to dogs should not exceed 10 mg/kg daily, as this produces therapeutic blood and tissue concentrations 25 (although current texts still recommend a dose rate up to 20 mg/kg daily).…”

“…25 Mild increases in ALP may be benign, although a substantially increased ALT signals the need to discontinue therapy. Some authors recommend that the dosage of rifampicin given to dogs should not exceed 10 mg/kg daily, as this produces therapeutic blood and tissue concentrations 25 (although current texts still recommend a dose rate up to 20 mg/kg daily). 26 Six dogs in the present study received dosages in the order of 10 to 15 mg/kg daily without any detectable sideeffects.…”

The Penetration of Dapsone, Rifampicin, Isoniazid and Pyrazinamide Into Peripheral Nerves

“…Preliminary experiments, in which single doses of the drugs were given to separate animals and plasma concentrations determined 1, 2, 4, 6 and 24 h later, revealed that in the dog the plasma half-life of isoniazid was about 4.5 h, pyrazinamide 5 h, rifampicin 10 h and DDS 18 hours. These values may be compared with estimates based on previously published data of 2.5, 5, 7-8 and 11 h, respectively (Peters, 1960;Cohn, 1969;Biggs, Gordon & Peters, 1971;Finkel, Pittillo & Mellett, 1971;Weiner & Tinker, 1972). Both DDS and isoniazid were acetylated by the sheep but neither compound was acetylated by the dog.…”

“…These values may be compared with estimates based on previously published data of 2.5, 5, 7-8 and 11 h, respectively (Peters, 1960;Cohn, 1969;Biggs, Gordon & Peters, 1971;Finkel, Pittillo & Mellett, 1971;Weiner & Tinker, 1972 (Mitchison, Allen & Miller, 1970).…”

Fluorometric Assay of Thioguanine

“…Fluorometry, which affords the required sensitivity and specificity, has been used in this laboratory for such analytical determinations (1)(2)(3)(4)(5). Very sensitive and specific assays are needed to determine the anticipated low concentrations of anticancer drugs and their metabolites in various biological systems.…”