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Population pharmacokinetics of pranlukast hydrate dry syrup in children with bronchial asthma


Susumu Nakade, Pharmacokinetic Research Laboratories, Minase Research Institute, Ono Pharmaceutical Co. Ltd, 3-1-1 Sakurai Shimamoto-cho Mishima-gun, Osaka 618-8585, Japan. Email:


Background:  This is the first report about the pharmacokinetics (PK) of pranlukast in children. The aim of the present study was to assess the PK parameters of pranlukast in children and to compare them with those in adults.

Methods:  Six healthy adult male volunteers and 22 children with bronchial asthma at 3−14 years of age were enrolled in the study. Both 225 and 112.5 mg pranlukast hydrate dry syrup was administered orally to adults, whereas 3.5 mg/kg pranlukast hydrate dry syrup was given to children. Blood samples were obtained at approximately 20 time points per adult (n = 121) and at two or three time points per child (n = 54). Population PK analysis was performed using nonmem (Globomax, Hanover, MD, USA). The concentration−time-course of pranlukast was described by using a one-compartment model with first-order absorption. The robustness of the final model was evaluated using 200 bootstrap samples.

Results:  Apparent clearance (CL/F) was 1.81 and 1.14 L/h per kg in children and adults, respectively. According to subgrouping of children, no significant difference was observed in CL/F between infants (3−6 years of age) and schoolchildren (7−14 years of age). The interindividual variability of CL/F accounted for 48.7%. The additive and proportional residual variability was 7.33 ng/mL and 73.8%, respectively. All fixed effect parameters fell within 10% of the bootstrapped mean.

Conclusions:  Compared with adults, children showed a higher CL/F and more rapid elimination after ingestion of pranlukast hydrate dry syrup. However, no significant variation was seen in CL/F between infants and schoolchildren.