Pharmacokinetics of oral tonapofylline and its acyl-glucuronide metabolite in patients with mild and moderate hepatic impairment
| Autor: | Kenneth C. Lasseter, Thomas Marbury, Daniel Freedman, Dong Wei, Liang-Shang Gan, Amy Natarajan, Aaron Deykin, Zhaoyang Li, Scott Stecher, Liyu Yang |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Metabolite Administration Oral Pharmacology Adenosine A1 Receptor Antagonists Gastroenterology Severity of Illness Index chemistry.chemical_compound Glucuronides Pharmacokinetics Internal medicine medicine Humans Pharmacology (medical) In patient Active metabolite Aged Volume of distribution Hepatic impairment Liver Diseases Capsule Middle Aged TONAPOFYLLINE chemistry Area Under Curve Case-Control Studies Xanthines Female Half-Life |
| Zdroj: | Journal of clinical pharmacology. 52(4) |
| ISSN: | 1552-4604 |
| Popis: | The objective of the study was to evaluate the effect of hepatic impairment on the pharmacokinetics of tonapofylline. Patients with mild or moderate hepatic impairment were enrolled in parallel with demographically matched healthy subjects. All study participants received a single 75-mg oral tonapofylline capsule. The pharmacokinetic parameters for both tonapofylline and its active metabolite, acyl-glucuronide (tonapofylline-AG), were affected by hepatic impairment significantly (P < .1) except for time to peak plasma concentration (t(max)), terminal half-life (t(½)), and apparent volume of distribution based on the terminal phase (Vdz/F). In the mild group, peak plasma concentration (C(max)), area under the time-concentration curve from time 0 to 48 hours postdose (AUC(48 h)), and from time 0 to infinity (AU(Cinf)) of tonapofylline modestly increased as compared with the control healthy subjects (GMR 1.62, 1.57, and 1.53, respectively). The extent of increase of these parameters for tonapofylline-AG was more profound than tonapofylline with geometric mean ratio (GMR) ranging from 2.02 to 2.08. Moderate hepatic impairment was also associated with modest increases of C(max), AUC(48 h), and AUC(inf) of tonapofylline (GMR 1.41, 1.98, and 2.08, respectively). Similar to the mild group, the increase of these parameters were higher for tonapofylline-AG with GMR ranging from 2.80 to 3.86. Single oral 75-mg tonapofylline was safe and well tolerated in patients with mild or moderate hepatic impairment. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text