Pharmacokinetics of Pentoxifylline and Its Main Metabolites in Patients With Different Degrees of Heart Failure Following a Single Dose of a Modified‐Release Formulation. (14th June 2013)

• Record Type: Journal Article
• Authors: Nisi, Alessandra; Panfili, Marco; De Rosa, Giovanni; Boffa, Giovanni; Groppa, Francesca; Gusella, Milena; Padrini, Roberto
• Is Part Of: Journal of clinical pharmacology. Volume 53:Number 1(2013:Jan.)
• Page Start: 51
• Page End: 57
• Publication Date: 2013-06-14
• Subjects: pentoxifylline -- chronic heart failure -- pharmacokinetics -- drug metabolism; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1177/0091270011433435
• Languages: English
• ISSNs: 0091-2700

Abstract

Abstract: Pentoxifylline (PTX) is extensively metabolized in the body, and all its 3 plasma metabolites (M1, M4, M5) are pharmacologically active. The authors evaluated the pharmacokinetics of PTX and its metabolites in 20 patients with chronic heart failure (CHF). Eleven had moderate and 9 severe CHF. The time courses of PTX, M1, M4, and M5 plasma levels were determined after oral administration of a sustained‐release 600‐mg tablet of PTX, and for each compound, AUC, maximal plasma concentration (Cmax ), and time to Cmax (Tpeak ) were calculated. Compared with patients with moderate CHF, those with severe CHF showed a significant delay in Tpeak of PTX (3.9 vs 1.6 hours) and M5 (5.6 vs 3.6 hours), a 59% significant increase in M5 AUC, and a 56% nonsignificant increase in PTX AUC. In the whole population, the AUCs of PTX, M4, and M5 were inversely correlated with markers of liver function, whereas the AUCs of M4 and M5 were inversely correlated with the creatinine clearance. In view of the kinetic features of slow‐release formulations (flip‐flop phenomenon), the delay in Tpeak of PTX in patients with severe CHF compared with moderate CHF should be ascribed to a reduced elimination rate.