desacetylcefotaxime and Body-Weight

To develop a pharmacostatistical model to simultaneously characterise the pharmacokinetics of cefotaxime and its main metabolite, desacetylcefotaxime, in elderly patients.. Cefotaxime, 1 g, was infused three times daily to 25 elderly patients, 66-93 years old. Cefotaxime and desacetylcefotaxime plasma concentrations (289 and 304 samples, respectively), along with demographic and physiological characteristics, were analysed using a population approach.. Cefotaxime pharmacokinetics was best described by a two-compartment open model in which desacetylcefotaxime was produced from the central compartment. The final parameter estimates were derived from simultaneous fit of parent/metabolite data. Cefotaxime clearance, mean 5.5 l/h, was positively influenced by body weight and serum protein concentration and negatively influenced by serum creatinine and age. In contrast, desacetylcefotaxime elimination was only decreased by age. The mean terminal half-lives of cefotaxime and desacetylcefotaxime were 1.7 h and 2.6 h, respectively. The stability and predictive performance of the final population pharmacokinetic model was assessed using 200 bootstrap samples of the original data.. Cefotaxime and desacetylcefotaxime elimination decreased with increasing age above 60 years. This decreased elimination was related to individual characteristics that are typically related to renal function.

Topics: Aged; Aged, 80 and over; Aging; Blood Proteins; Body Weight; Cefotaxime; Drug Administration Schedule; Female; France; Geriatric Assessment; Half-Life; Humans; Infusions, Intravenous; Inpatients; Kidney; Male; Models, Biological; Time Factors

Cefotaxime sodium (1 g) was injected intravenously in 12 normal (90-110% ideal body weight) and 11 obese (190-210% ideal body weight) male and female subjects. Plasma and urine levels were measured for cefotaxime and its active metabolite desacetylcefotaxime. Kinetic parameters were calculated. Results indicate that a dose adjustment for body weight in obese subjects is not needed, whereas a dose adjustment on the basis of body surface area is reasonable. Metabolite plasma levels in female subjects were significantly higher than in male subjects in both the normal and the obese populations.

Topics: Body Surface Area; Body Weight; Cefotaxime; Female; Humans; Injections, Intravenous; Kinetics; Male; Mathematics; Obesity; Sex Factors