title: Pharmacokinetics and pharmacodynamics of orally administered clonidine: a model-based approach.
abstract: OBJECTIVE
  The oral clonidine test is a diagnostic procedure performed in children with suspected growth hormone (GH) deficiency. It is associated with untoward effects, including bradycardia, hypotension and sedation. Serum clonidine levels have not previously been assessed during this test.
  
  
  METHODS
  In 40 children referred for an oral clonidine test, blood samples were drawn for clonidine and GH. Vital statistics and sedation scores were recorded until 210 min post-dose. We explored the relationship between clonidine concentrations and effects such as GH peak and blood pressure.
  
  
  RESULTS
  Of 40 participants, 5 children were GH deficient. Peak clonidine concentrations of 0.846 ± 0.288 ng/ml were reached after 1 h. Serum levels declined slowly, with concentrations of 0.701 ± 0.189 ng/ml 210 min post-dose. A large interindividual variation of serum levels was observed. During the procedure, systolic blood pressure dropped by 12.8%, diastolic blood pressure by 19.7% and heart rate by 8.4%. Moderate sedation levels were observed. Concentration-effect modeling showed that the amount of GH available for secretion as determined by previous bursts was an important factor influencing GH response.
  
  
  CONCLUSIONS
  Clonidine concentrations during the test were higher than necessary according to model-based predictions. A lower clonidine dose may be sufficient and may produce fewer side effects.
authors.affiliation: Centre for Human Drug Research, Leiden University Medical Center, NL-2300 RC Leiden, The Netherlands. r.h.klein@lumc.nl
authors.forename: R H
authors.initials: RH
authors.lastname: Klein
authors.forename: R
authors.initials: R
authors.lastname: Alvarez-Jimenez
authors.forename: R N
authors.initials: RN
authors.lastname: Sukhai
authors.forename: W
authors.initials: W
authors.lastname: Oostdijk
authors.forename: B
authors.initials: B
authors.lastname: Bakker
authors.forename: H M
authors.initials: HM
authors.lastname: Reeser
authors.forename: B E P B
authors.initials: BE
authors.lastname: Ballieux
authors.forename: P
authors.initials: P
authors.lastname: Hu
authors.forename: E S
authors.initials: ES
authors.lastname: Klaassen
authors.forename: J
authors.initials: J
authors.lastname: Freijer
authors.forename: J
authors.initials: J
authors.lastname: Burggraaf
authors.forename: A F
authors.initials: AF
authors.lastname: Cohen
authors.forename: J M
authors.initials: JM
authors.lastname: Wit
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003000:Clonidine / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency; D006801:Humans; D008297:Male; D008954:Models, Biological; D013565:Sympatholytics / Q000008:administration & dosage / Q000493:pharmacokinetics; D013997:Time Factors
chemical_list: D013565:Sympatholytics; D019382:Human Growth Hormone; D003000:Clonidine