Phase I pharmacokinetic study of a new 3-azinomethyl-rifamycin (rifametane) as compared to rifampicin.
An open randomized cross-over study was conducted in 8 healthy male volunteers to study the pharmacokinetic pattern and the safety of a 300-mg single oral dose of a new 3-azinomethyl-rifamycin (USAN rifametane, SPA-S-565) compared with 300 mg of conventional rifampicin. The pharmacokinetic profiles of rifametane were significantly more favorable than those of rifampicin. The serum peak value was 7.82 microg/ml for rifametane and 4.04 microg/ml for rifampicin (p < 0.001); the elimination half-life was 10.58 h for rifametane and 1.89 h for rifampicin (p < 0.001); area under the serum concentration curve from 0 to infinity was 142.3 microg.h/ml for rifametane and 19.9 microg.h/ml for rifampicin (p < 0.001); the mean residence time was 18.05 h for rifametane and 3.93 h for rifampicin (p < 0.001). Rifametane showed a good safety profile after the 300-mg single oral dose. Three volunteers developed a mild headache, metallic taste and slightly elevated temperature for 3-4 h, which subsided without medication. Clinically or statistically significant changes in laboratory parameters were not found between baseline and posttreatment values.
Potkar
C
C
Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Bombay, India.
Gogtay
N
N
Gokhale
P
P
Kshirsagar
N A
NA
Ajay
S
S
Cooverji
N D
ND
Bruzzese
T
T
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D012016:Reference Values; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D012294:Rifamycins / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*
D000904:Antibiotics, Antitubercular; D012294:Rifamycins; C058615:rifametane; D012293:Rifampin