Effect of age on cis-atracurium besylate pharmacokinetics following a single 1 mg kg–1 intravenous bolus in young pigs

Abstract

ObjectiveTo determine the cis-atracurium pharmacokinetic data and laudanosine production of a single 1 mg kg–1 cis-atracurium dose in the pig and to compare the pharmacokinetics between two groups of different ages. Study designProspective experimental study. AnimalsSixteen female pigs in two groups. Group A included eight animals aged 2.0–2.5 months and weighed 26.6 ± 3.6 kg. Group B included eight animals aged 4.0–5.0 months and weighed 57.4 ± 8.3 kg. MethodsThe pigs were anaesthetized and monitored throughout the procedure. Arterial blood samples collected at 0, 0.5, 1, 2, 5, 10, 20, 30, 45, 60, 90, 120 and 180 minutes after cis-atracurium injection were cooled and centrifuged. Plasma was acidified and stored at –20 °C for subsequent cis-atracurium and laudanosine analyses. ResultsAnaesthetic parameters were within normal ranges throughout the procedure. Plasma cis-atracurium and laudanosine concentrations were measured for the 16 pigs. Elimination rate constant, elimination half-life, area under the curve, mean residence time, distribution volume and total clearance were calculated for each pig. Statistical differences (p < 0.05) in the elimination rate constant, elimination half-life, mean residence time and distribution volume values were observed between the two groups. Elimination half-life, mean residence time and distribution volume values were higher and elimination rate constant lower in younger pigs than in older pigs. No plasma laudanosine concentrations were detected in any pig. Conclusion and clinical relevanceLonger duration of plasma cis-atracurium concentrations were observed in younger pigs. Distribution volume was also higher in younger pigs. Conversely, total clearance and area under the curve were similar between the two age groups. No laudanosine production was detected, suggesting a different cis-atracurium metabolism in the pig compared with other species.