title: Population pharmacokinetics of tamsulosin hydrochloride in paediatric patients with neuropathic and non-neuropathic bladder.
abstract: BACKGROUND
  Tamsulosin is available on prescription as a modified release capsule in the US (Flomax), and in most European countries for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). The pharmacokinetics of tamsulosin hydrochloride (HCl) have been extensively studied in adults, but no pharmacokinetic data for paediatrics have been published to date.
  
  
  CONCLUSIONS
  A population pharmacokinetic model of tamsulosin HCl was developed in paediatric patients. Covariate analysis revealed that body weight and alpha(1)-acid glycoprotein influenced both the apparent clearance and the apparent volume of distribution. This study confirms that there is no major difference in the pharmacokinetics of tamsulosin HCl between paediatrics (age range 2-16 years) and adults when the effect of body weight is taken into consideration.
  
  
  OBJECTIVE
  The main objective of this study was to characterize the population pharmacokinetics of tamsulosin hydrochloride (HCl) in paediatric patients with neuropathic and non-neuropathic bladder. A secondary objective was to compare the pharmacokinetics in paediatric patients and adults.
  
  
  METHODS
  Tamsulosin HCl plasma concentrations in 1082 plasma samples from 189 paediatric patients (age range 2-16 years) were analyzed with NONMEM, applying a one compartment model with first-order absorption. Based on the principles of allometry, body weight was incorporated in the base model, along with fixed allometric exponents. Covariate analysis was performed by means of a stepwise forward inclusion and backward elimination procedure. Simulations based on the final model were used to compare the pharmacokinetics with those in adults.
  
  
  RESULTS
  Beside the priori-implemented body weight, only alpha(1)-acid glycoprotein had an effect on both apparent clearance and apparent volume of distribution. No other investigated covariates, including gender, age, race, patient population and concomitant therapy with anti-cholinergics, significantly affected the pharmacokinetics of tamsulosin HCl (P < 0.001). The results of simulations indicated that the exposure in 12.5 kg paediatric patients was 3.5-4.3 fold higher than that in 70.0 kg adults. After a weight-based dose administration, the exposure in paediatric patients was comparable with that in healthy adults.
  
  
  CONCLUSIONS
  A population pharmacokinetic model of tamsulosin HCl in paediatric patients was established and it described the data well. There was no major difference in the pharmacokinetics of tamsulosin HCl between paediatric patients (age range 2-16 years) and adults when the effect of body weight was taken into consideration.
authors.affiliation: Pharmacokinetics and Non-Clinical Safety Department, Nippon Boehringer Ingelheim Co., Ltd, Hyogo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsuda
authors.forename: Shinji
authors.initials: S
authors.lastname: Tatami
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamura
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tadayasu
authors.forename: Akiko
authors.initials: A
authors.lastname: Sarashina
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Liesenfeld
authors.forename: Alexander
authors.initials: A
authors.lastname: Staab
authors.forename: Hans-Günter
authors.initials: HG
authors.lastname: Schäfer
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ieiri
authors.forename: Shun
authors.initials: S
authors.lastname: Higuchi
mesh_terms: D000293:Adolescent; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001835:Body Weight / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D009961:Orosomucoid; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077409:Tamsulosin; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy*
chemical_list: D000317:Adrenergic alpha-Antagonists; D009961:Orosomucoid; D013449:Sulfonamides; D000077409:Tamsulosin