AimsTo study the pharmacokinetics of vigabatrin in a patient affected with tuberous sclerosis who developed major agitation and aggression, while receiving vigabatrin orally (1.5 g every 12 h) and in whom impaired renal function was diagnosed. Methods The patient received vigabatrin (0.5 g day −1 ). A pharmacokinetic study of the S(+) and R(−) enantiomers of vigabatrin was performed before and during dialysis. Plasma concentrations were measured at 0, 1, 2, 3, 4, 6, 12, 18 and 24 h by a specific GCMS assay. Results Before dialysis, the maximum and minimun plasma concentrations of vigabatrin at steady-state were lower for the S(+) than for the R(−) enantiomer, while the apparent oral clearance was higher for the S(+) than for the R(−) enantiomer (2.97 vs 0.48 l h −1 ). In addition, the haemodialysis clearance was similar for the two enantiomers (4.96 vs 5.15 l h −1 ).
ConclusionsVigabatrin is an irreversible inhibitor of GABA-transaminase, effective in the treatment of drug-resistant epilepsy and reported to be eliminated unchanged by renal excretion. Although vigabatrin is known to have stereoselective kinetics, the difference in plasma dry concentrations and pharmacokinetics of the S(+) and R(−) enantiomers that we observed during long term administration at high doses in a patient with impaired renal function, has not been reported before. The question remains of the potential toxicity of the high levels of the R(−) enantiomer.
The objective of this article is to describe the conditions under which very premature babies were born in the Paris region between June 1 and December 31, 1998, that is to say those born prior to reaching 33 weeks of term (SA) and/or having a birth weight less than 1500 grams. The study looked at all pre-term births, including medical terminations of pregnancy (TOP), occurring in one of the 135 maternity units in the Paris region. Between June 1 and December 31, 1998, 1337 mothers gave birth to babies prior to reaching 33 weeks of term (SA) and/or having a birth weight less than 1500 grams in 84 maternity units in the Paris region, 263 of which had a medical termination of pregnancy (20%). These mothers were older than average for the region (25% were 35 years old or older); 4.3% of them do not have social insurance coverage. The remaining 1074 mothers (excluding TOP) gave birth to 1290 children, of which 202 were stillbirths, 46 died in the labor ward and 1042 were admitted to a neo-natal unit. Of the same group of 1074 mothers, 195 (18%) had a multiple pregnancy--175 twins, 19 triplets, and 1 quadruplet 60% of them (599 women) who had very premature or low birth weight babies (excluding TOPs) delivered them in a tertiary perinatal centre (TPC). This proportion varies according to two variables: 1) the community in which the family lives (40% in the Seine-et-Marne department, the eastern region of Paris and a district without TPCs, to 70% in the Hauts-de-Seine, a northern district), and 2) whether the pregnancy is single (58.8%), twin (72.6%) or triple (84.2%). In utero transfer accounts for 62.7% of the mothers who delivered in TPC, who were transferred prior to delivery. This type of study is useful for measuring the implementation of the regionalisation high-risk perinatal care and access to adequate services. It clearly demonstrates that inequities in access to care exist for women by district of residence.
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