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Capreomycin is not absorbed in significant quantities from the gastrointestinal tract and must be administered parenterally. In 2 studies of 10 patients each, peak serum concentrations following 1 g of capreomycin given intramuscularly were achieved 1 to 2 hours after administration, and average peak levels reached were 28 and 32 µg/mL respectively (range, 20 to 47 µg/mL). Low serum concentrations were present at 24 hours. However, 1 g of capreomycin daily for 30 days or more produced no significant accumulation in subjects with normal renal function. Two patients with marked reduction of renal function had high serum concentrations 24 hours after administration of the drug. When a 1-g dose of capreomycin was given intramuscularly to normal volunteers, 52% was excreted in the urine within 12 hours.
Lehmann, et al, examined the pharmacokinetics of single dose capreomycin (1.0 g) administered intramuscularly and by intravenous infusion (1 hour) in 6 healthy volunteers. The area under the serum concentration versus time curve was similar for the two routes of administration. Capreomycin peak concentrations after intravenous infusion were 30 ± 47% higher than after intramuscular administration.1,2
Paper chromatographic studies indicated that capreomycin is excreted essentially unaltered. Urine concentrations averaged 1.68 mg/mL (average urine volume, 228 mL) during the 6 hours following a 1-g dose.
Capreomycin is active against strains of Mycobacterium tuberculosis found in humans.
The in vitro susceptibility of strains of M. tuberculosis to capreomycin varies with the media and techniques employed. In general, the minimum inhibitory concentrations for M. tuberculosis are lowest in liquid media that are free of egg protein (7H10 or Dubos) and range from 1 to 5 µg/mL when the indirect method is used. Comparable inhibitory concentrations are obtained when 7H10 agar is used for direct susceptibility testing. When indirect susceptibility tests are performed on standard tube slants with 7H10 media, susceptible strains are inhibited by 10 to 25 µg/mL capreomycin. Egg-containing media, such as Löwenstein-Jensen or ATS, require concentrations of 25 to 50 µg/mL to inhibit susceptible strains.
Frequent cross-resistance occurs between capreomycin and viomycin. Varying degrees of cross-resistance between capreomycin and kanamycin and neomycin have been reported. No cross-resistance has been observed between capreomycin and isoniazid, aminosalicylic acid, cycloserine, streptomycin, ethionamide, or ethambutol.
In addition to renal and cranial nerve VIII toxicity demonstrated in animal toxicology studies, cataracts developed in 2 dogs on doses of 62 mg/kg and 100 mg/kg for prolonged periods.
In teratology studies, a low incidence of "wavy ribs" was noted in litters of female rats treated with daily doses of 50 mg/kg or more of capreomycin.
1. Lehmann CR, Garrett LE, Winn RE, Springberg PD, Vicks S, Porter DK, Pierson WP, Wolny JD, Brier GL, Black HR. Capreomycin kinetics in renal impairment and clearance by hemodialysis. Am Rev Respir Dis 1988;138/5:1312-3.
2. Unpublished data on file at Lilly.
Last reviewed on RxList: 9/4/2008
This monograph has been modified to include the generic and brand name in many instances.
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