ISSN:
1432-1041
Keywords:
netilmicin
;
aminoglycoside antibiotics
;
nephrotoxicity
;
pharmacokinetics
;
multiple dose
;
i.m. route
;
individual variability
;
absorption
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Summary Intra- and interindividual variability in the serum kinetics and renal elimination of netilmicin was investigated in a controlled study in 6 healthy, male volunteers. The antibiotic was administered on 2 single days, separated by a 3 week interval. Netilmicin 2 mg/kg lean body mass was given i.m. twice (b.i.d.) and three times (t.i.d.) in a crossover design. 54 blood and 28 urine samples per volunteer were analysed by a radio-enzymatic assay. 24 h serum kinetics were best described by a two compartment open model with time-dependent serum clearance. The latter decreased intraindividually on both study days, from a mean of 82 to 68 ml/min (p〈0.05). A similar decrease was observed in the 12 h creatinine clearance. Because drug administration started in the morning, this finding reflects the physiological circadian rhythm in the glomerular filtration rate. The corresponding half-lives of netilmicin rose from 149 to 171 min. Striking intraindividual variation in absorption half-life was observed in all volunteers, ranging from less than 4 to more than 30 min. Comparison of the pharmacokinetic parameters derived from data of the first and second study, revealed a significant intraindividual reduction in the volume of distribution (mean decrease 13%) and in the serum clearance of netilmicin (−8%). Analysis of the serum data of the b.i.d. and t.i.d. dosing schedules showed no difference in the pharmacokinetic parameters; there was significantly higher urinary recovery with the t.i.d. (+9%) than with the b.i.d. schedules. After both days, the 24 h creatinine clearance decreased significantly, by more than 10%. A slight nephrotoxic effect, induced by a therapy for one day with netilmicin, can be deduced from these data.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00610062
