PHARMACOKINETICS OF PIPECURONIUM IN INFANTS, CHILDREN AND ADULTS

In order to explain the reported shorter clinical duration of action of 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 children (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 blood was sampled for 4-5 h. Pipecuronium was quantified by complex formation with [I-125]-labelled rose bengal. Pharmacokinetic parameters were calculated using a two-compartment open model. The median for the distribution half-life of pipecuronium was 2.54 min (interquartile range: 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). The plasma clearance of pipecuronium was significantly decreased in infants (1.50 [0.6-1.5] ml.min(-1).kg(-1); P < 0.05) as compared to children 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 three groups. We conclude that the pharmacokinetic features of pipecuronium are age-dependent: differences as compared to adults consisted of a faster distribution in both infants and children and a slower elimination 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 infants, pipecuronium dosage should be carefully monitored to avoid accumulation and prolonged paralysis.