Elimination kinetics of thiopentone in mothers and their newborn infants

Abstract

The elimination kinetics of thiopentone was studied in 7 newborns delivered by Caesarean section and in their mothers who had received the drug for induction of anaesthesia. At delivery, 4-9 min after induction, drug concentrations in cord blood were half those in material blood. The mean half-life of thiopentone in the newborns was about double that in their mothers (15 vs 7 h) confirming a disposition similar to other barbiturates. For the first time renal clearance of thiopentone was estimated in the newborn; 0.074 ml/h/kg. Only 0.0007% (about 2 micrograms) of the maternal dose was recovered in the urine of newborns over 36 h. Pentobarbitone, an active metabolite, was not detected in any specimen. The findings demonstrate the reliability of current anaesthesiological technique (thiopentone-succinylcholine-oxygen) with minimal fetal exposure to the drug.

8‐Substituted Xanthines as Phosphodiesterase Inhibitors: Conformation‐Dependent Lipophilicity and Structure‐Activity Relationships

“…marked, minute, and nil for Me-N( l), Me-N(3), and Me-N(7), resp.). Electronic and intermolecular H-bonding effects were postulated [7]. While such effects may be operative in the compounds studied here, their contribution is partial at best.…”

“…Gaspari and Bonati [7] have shown that in N-methylated xanthines, the three Me groups make different contributions to the lipophilicity of the molecule (i.e. marked, minute, and nil for Me-N( l), Me-N(3), and Me-N(7), resp.).…”

“…There are abundant reports in the literature exemplifying excellent correlations between retention on RP-HPLC (log k: values) and measured or calculated octanol/H,O partition coefficients (log P ) (e.g. [4] [7]. pK, of the base.…”

Isotope Effects on the Lipophilicity of Deuterated Caffeines

“…In this context, it is of interest to note that Gaspari and Bonati [30] have recently shown that in methylated xanthines the lipophilic contribution of N-methyl groups as compared to NH groups is highly position-dependent ; while CH,-N( 1) markedly contributes to lipophilicity, CH,-N(3) and CH,-N(7) have little or no effect. These authors also found that the additivity rule applied only to the 1,7-dimethylation pattern, a result in keeping with the isotope effect in (l,7-dimethyl-2H,)caffeine.…”

“…These authors also found that the additivity rule applied only to the 1,7-dimethylation pattern, a result in keeping with the isotope effect in (l,7-dimethyl-2H,)caffeine. Steric and electronic effects were postulated to account for these differences [30] (see Discussion).…”