BACKGROUND AND OBJECTIVE: Pharmacokinetic studies using deconvolution methods and non-compartmental analysis to model clinical absorption of drugs are not well represented in the literature. The purpose of this research was (1) to define the system of equations for description of rotigotine (a dopamine receptor agonist delivered via a transdermal patch) absorption based on a pharmacokinetic model and (2) to describe the kinetics of rotigotine disposition after single and multiple dosing. METHODS: The kinetics of drug disposition was evaluated based on rotigotine plasma concentration data from three phase 1 trials. In two trials, rotigotine was administered via a single patch over 24 h in healthy subjects. In a third trial, rotigotine was administered once daily over 1 month in subjects with early-stage Parkinson's disease (PD). A pharmacokinetic model utilizing deconvolution methods was developed to describe the relationship between drug release from the patch and plasma concentrations. Plasma-concentration over time profiles were modeled based on a one-compartment model with a time lag, a zero-order input (describing a constant absorption via skin into central circulation) and first-order elimination. Corresponding mathematical models for single- and multiple-dose administration were developed. RESULTS: After single-dose administration of rotigotine patches (using 2, 4 or 8 mg/day) in healthy subjects, a constant in vivo absorption was present after a minor time lag (2-3 h). On days 27 and 30 of the multiple-dose study in patients with PD, absorption was constant during patch-on periods and resembled zero-order kinetics. CONCLUSION: Deconvolution based on rotigotine pharmacokinetic profiles after single- or multiple-dose administration of the once-daily patch demonstrated that in vivo absorption of rotigotine showed constant input through the skin into the central circulation (resembling zero-order kinetics). Continuous absorption through the skin is a basis for stable drug exposure.
BACKGROUND AND OBJECTIVE: Pharmacokinetic studies using deconvolution methods and non-compartmental analysis to model clinical absorption of drugs are not well represented in the literature. The purpose of this research was (1) to define the system of equations for description of rotigotine (a dopamine receptor agonist delivered via a transdermal patch) absorption based on a pharmacokinetic model and (2) to describe the kinetics of rotigotine disposition after single and multiple dosing. METHODS: The kinetics of drug disposition was evaluated based on rotigotine plasma concentration data from three phase 1 trials. In two trials, rotigotine was administered via a single patch over 24 h in healthy subjects. In a third trial, rotigotine was administered once daily over 1 month in subjects with early-stage Parkinson's disease (PD). A pharmacokinetic model utilizing deconvolution methods was developed to describe the relationship between drug release from the patch and plasma concentrations. Plasma-concentration over time profiles were modeled based on a one-compartment model with a time lag, a zero-order input (describing a constant absorption via skin into central circulation) and first-order elimination. Corresponding mathematical models for single- and multiple-dose administration were developed. RESULTS: After single-dose administration of rotigotine patches (using 2, 4 or 8 mg/day) in healthy subjects, a constant in vivo absorption was present after a minor time lag (2-3 h). On days 27 and 30 of the multiple-dose study in patients with PD, absorption was constant during patch-on periods and resembled zero-order kinetics. CONCLUSION: Deconvolution based on rotigotine pharmacokinetic profiles after single- or multiple-dose administration of the once-daily patch demonstrated that in vivo absorption of rotigotine showed constant input through the skin into the central circulation (resembling zero-order kinetics). Continuous absorption through the skin is a basis for stable drug exposure.
Authors: G Lefèvre; G Sedek; S S Jhee; M T Leibowitz; H-La Huang; A Enz; S Maton; L Ereshefsky; F Pommier; H Schmidli; S Appel-Dingemanse Journal: Clin Pharmacol Ther Date: 2007-05-23 Impact factor: 6.875
Authors: Glenn A Van Buskirk; Daniel Arsulowicz; Prabir Basu; Lawrence Block; Bing Cai; Gary W Cleary; Tapash Ghosh; Mario A González; David Kanios; Margareth Marques; Patrick K Noonan; Terrance Ocheltree; Peter Schwarz; Vinod Shah; Thomas S Spencer; Lino Tavares; Katherine Ulman; Rajendra Uppoor; Thean Yeoh Journal: AAPS PharmSciTech Date: 2012-01-04 Impact factor: 3.246
Authors: Claudia Trenkwalder; Bryan Kies; Monika Rudzinska; Jennifer Fine; Janos Nikl; Krystyna Honczarenko; Peter Dioszeghy; Dennis Hill; Tim Anderson; Vilho Myllyla; Jan Kassubek; Malcolm Steiger; Marco Zucconi; Eduardo Tolosa; Werner Poewe; Erwin Surmann; John Whitesides; Babak Boroojerdi; Kallol Ray Chaudhuri Journal: Mov Disord Date: 2010-11-18 Impact factor: 10.338
Authors: Alison Margolskee; Adam S Darwich; Aleksandra Galetin; Amin Rostami-Hodjegan; Leon Aarons Journal: AAPS J Date: 2015-12-14 Impact factor: 4.009