PHARMACOKINETICS OF PIPECURONIUM IN INFANTS, CHILDREN AND ADULTS

In order to explain the reported shorter clinical duration of action o f cumulative ED(95) of pipecuronium in infants as compared to children or adults. the pharmacokinetic profiles of pipecuronium were compared in infants (n = 6; mean age 6.8 months; mean weight 7.3 kg) in childr en (n = 6: mean age 4.6 years: mean weight 19.2 kg) and in adults (n = 7; mean age 42 years; mean weight 58.2 kg). Equipotent doses (2 x ED( 95)) of pipecuronium were injected i.v. as single bolus and arterial b lood was sampled for 4-5 h. Pipecuronium was quantified by complex for mation with [I-125]-labelled rose bengal. Pharmacokinetic parameters w ere calculated using a two-compartment open model. The median for the distribution half-life of pipecuronium was 2.54 min (interquartile ran ge: 1.0-2.5 min) in infants and 2.04 min (0.26-2.04 min) in children; both were significantly shorter than in adults (5.75 [3.7-9.7] min). T he plasma clearance of pipecuronium was significantly decreased in inf ants (1.50 [0.6-1.5] ml.min(-1).kg(-1); P < 0.05) as compared to child ren and adults (2.27 [0.88-2.27] and 2.45 [1.7-3.2] ml.min(-1).kg(-1), respectively). The total volume of distribution was similar in all th ree groups. We conclude that the pharmacokinetic features of pipecuron ium are age-dependent: differences as compared to adults consisted of a faster distribution in both infants and children and a slower elimin ation in infants. The pharmacokinetic profile of pipecuronium does not explain the faster recovery from neuromuscular blockade in infants as compared to children. Because of the low total plasma clearance in in fants, pipecuronium dosage should be carefully monitored to avoid accu mulation and prolonged paralysis.