Placental transfer and neonatal effects of propofol in caesarean section.

OBJECTIVE: To assess transplacental passage of propofol by measuring the levels in maternal and foetal plasma, and the possible relationship between the latter and the neonatal effects when propofol is used as an induction agent in obstetric anaesthesia for performing a caesarean section to terminate pregnancy. METHODS: Intravenous propofol was administered as an anaesthesia-inducing agent at doses of 2 mg/kg in 10 healthy women (ASA I-II). The propofol concentrations were measured by high-performance liquid chromatography (HPLC). RESULTS: After induction, hypnosis was achieved in all patients within 75 s, and it took 4-10 min to deliver the foetus. Apgar test scores were high in seven of the 10 neonates, in three cases the score was 5 or less. The mean values in venous maternal blood were 5.01+/-1.06 microg/ml 1 min after propofol administration and 1.47+/-0.35 microg/ml at the time of delivery. Propofol crossed the placental barrier with levels in the umbilical cord of 0.32+/-0.10 microg/ml in the vein and 0.22+/-0.08 microg/ml in the artery. CONCLUSION: Propofol plasma levels in the newborn at the time of delivery depend on the level in maternal plasma, and therefore on the dose used for induction and the time lapsed between the administration of the drug and the delivery of the foetus.

Valproic acid clearance in children with epilepsy.

OBJECTIVE: To evaluate population pharmacokinetics and the relationship between plasma concentration and daily dose of valproic acid (VPA) in a homogeneous group of children with epilepsy. METHODS: One hundred and fifty-one steady-state VPA plasma level measurements were made in 62 children aged 8 months to 6 years who were receiving VPA monotherapy. RESULTS: The level:dose ratio increased with age, its mean value was 1.7 in children aged under 2 years, 2.1 in children aged 2.4 years and 3.3 in children aged 4.6 years. Weight-adjusted values of VPA clearance (Cl) decreased with increasing age. The Cl values in these three age groups were 24.5+/-12.4 ml/kg/h, 19.9+/-6.1 ml/kg/h and 12.7+/-3.0 ml/kg/h, respectively. The relationship between VPA clearance and age was: Cl (ml/kg/h)=47.6 x age (months)(-0.29), (r=-0.87). This equation allows the estimation of VPA plasma clearance on the basis of the child's age, within the range 8-72 months. Therefore, it can be used to establish the initial maintenance paediatric dose of VPA in monotherapy. CONCLUSION: The relationship between clearance and age should be useful when establishing a pharmacokinetic programme for VPA monotherapy in children.

Therapeutic drug monitoring of tobramycin: once-daily versus twice-daily dosage schedules.

OBJECTIVE: To evaluate the effect of dosage regimen (once-daily vs. twice-daily) of tobramicyn on steady-state serum concentrations and toxicity. MATERIALS AND METHODS: Patients undergoing treatment with i.v. tobramycin (4 mg/kg/day) were randomised to two groups. Group OD (n = 22) received a once-daily dose of tobramycin and group TD (n = 21) received the same dose divided into two doses daily. Tobramycin serum concentrations (peak and trough) were measured by enzyme multiplied immunoassay. The renal and auditory functions of the patients were monitored before, during and immediately after treatment. RESULTS: The two groups were comparable with respect to sex, age, body weight and renal function. No statistically significant differences were found in mean daily dose, duration of treatment, or cumulative dose. Trough concentrations were < 2 g/ml in the two groups (100%). Peak concentrations were > 6 microg/ml in 100% of the OD group and in 67% of the TD group (P< 0.01). Mean peak concentrations were markedly different: 11.00+/-2.89 microg/ml in OD vs. 6.53+/-1.45 microg/ml in TD (P< 0.01). The pharmacokinetics parameters were: Ke, (0.15+/-0.03/h in OD vs. 0.24+/-0.06/h in TD), t1/2, (4.95+/-1.41 h in OD vs. 3.07+/-0.71 h in TD), Vd (0.35+/-0.11 l/kg in OD vs. 0.33+/-0.09 l/kg in TD), Cl (0.86+/-0.29 ml/min/kg in OD vs. 1.28+/-0.33 ml/min/kg in TD). Increased serum creatinine was observed in 73% of patients in OD versus 57% of patients in TD, without evidence of nephrotoxicity. In TD group, three patients developed decreased auditory function, of which one presented with an auditory loss of -30 dB, whereas in the OD group only one patient presented decreased auditory function. CONCLUSION: This small study suggests that a once-daily dosing regimen of tobramycin is at least as effective as and is no more and possibly less toxic than the twice-daily regimen. Using a single-dose therapy, peak concentration determination is not necessary, only trough samples should be monitored to ensure levels below 2 microg/ml.