Pharmacokinetics of a new macrolide, roxithromycin, in infants and children.

The pharmacokinetics of roxithromycin was investigated after oral administration of 2.5 mg/kg doses given 12 hours apart during 6 days in infants and children. These 18 subjects suffering from a respiratory tract infection were divided into three age groups: group I less than 18 months, group II less than 5 years, group III less than 13 years. At day 6, the elimination plasma half-life had an average value (mean +/- SD) of 19.8 +/- 9.7 h (group I), 21.0 +/- 9.4 h (group II) and 20.8 +/- 6.9 h (group III), respectively. The maximum concentration of roxithromycin (Cmax) was attained between 1 and 2 hours after dosing with mean values of 10.1 +/- 3.0 mg/l (group I), 8.7 +/- 4.9 mg/l (group II), 8.8 +/- 7.0 mg/l (group III). All the calculated pharmacokinetic parameters did not significantly differ from one group to another. The kinetics of roxithromycin in infants and children seemed to be age independent and showed no accumulation after repeated doses. During 12 hours, the plasma concentrations were above MIC of microorganisms generally present in respiratory tract infections. Two daily doses of 2.5 mg/kg of roxithromycin 12 hours apart may be proposed in infants and children.

Micromethod for determination of ceftriaxone in plasma and urine by high-performance liquid chromatography.

A sensitive and rapid high-performance liquid chromatographic method for the determination of ceftriaxone in human plasma and urine is described. A C18 reversed phase column is used; the mobile phase comprises water-methanol-triethylamine (750:250:4v/v/v) adjusted to pH 3 with orthophosphoric acid. Quantitation is performed at 270 nm with cefazolin as the internal standard. This method involves precipitation of proteins from fluids with acetonitrile followed by extraction of endogenous compounds with chloroform and injection of the upper aqueous phase on to the chromatograph. Relative standard deviations for between-day and within-day assays are 6.2%. The detection limit is 0.5 microg(-1) in plasma and urine. Studies of drug stability during sample storage, sample pretreatment and chromatography showed no degradation of ceftriaxone or of the internal standard. The method is convenient for clinical monitoring and for pharmacokinetic studies.

Imipramine blood levels and clinical outcome.

Fifty-one depressed inpatients, after 1 drug-free week, were treated for 5 weeks with imipramine 4 mg/kg day. Plasma levels of imipramine (IMI) and its active metabolite desmethylimipramine (DMI) were measured weekly, 15 hours after the last drug intake. Steady state blood levels (IMI + DMI) ranged from 60 to 585 ng/ml. The mean value for plasma concentration (IMI + DMI) at day 42 was 271 ng/ml. In the same way, therapeutic effectiveness was assessed every week using the Hamilton Rating Scale for Depression (HDRS). There was a significant correlation between plasma concentration and the decrease of Hamilton scores. The IMI/DMI ratio showed a responder-nonresponder difference; 86% patients with a ratio between 0.4 and 1 were responders. Conversely, most patients with a ratio below 0.4 or above 1 were nonresponders. The ideal ratio for clinical response would be 0.68. The ratio is a subject-specific feature, able to be an early predictor of clinical outcome.

Pharmacokinetics of intravenous and intraperitoneal cefotaxime in chronic ambulatory peritoneal dialysis.

We investigated the kinetics of cefotaxime in eight subjects undergoing continuous ambulatory peritoneal dialysis (CAPD). A single 1 gm iv dose was injected and a 1 gm dose was given intraperitoneally in the CAPD fluid during a 4-hour dwell time. Cefotaxime and desacetylcefotaxime were assayed by HPLC. After intravenous injection the cefotaxime serum kinetic parameters were as follows: plasma t 1/2, 2.31 +/- 0.20 hours; volume of distribution, 0.35 +/- 0.04 L/kg; total plasma clearance, 118.7 +/- 12.3 ml/min; and peritoneal clearance, 6.7 +/- 1.3 ml/min. Dialysate cefotaxime concentrations rose rapidly, but only 5% of the dose was eliminated by the peritoneal route. After intraperitoneal instillation, cefotaxime appeared in the serum rapidly and the peak serum concentrations ranged from 9 to 20 micrograms/ml between 1 and 3 hours. The absorption of cefotaxime from peritoneal space was 58.7% +/- 5.4%. Data suggest that cefotaxime has bidirectional exchange characteristics through the peritoneal membrane. Instillation of cefotaxime in CAPD fluid may permit rapid absorption to achieve therapeutic serum concentrations.