Rimantadine pharmacokinetics after single and multiple doses

Abstract

Twenty-four healthy adult male volunteers were randomly assigned to one of two rimantadine regimens. The 12 volunteers assigned to regimen 1 orally received a single 100-mg rimantadine tablet followed 5 days later by 100 mg of rimantadine twice a day for 10 days. Volunteers assigned to regimen 2 ingested a single 100-mg rimantadine tablet followed 5 days later by 100 mg once a day for 10 days. The results of the study suggest that the pharmacokinetics of rimantadine are linear and accumulation of the drug during repetitive multiple doses is predictable.

Multiple-dose pharmacokinetics of rimantadine in elderly adults

“…In addition, the pharmacokinetics of rimantadine during repetitive dosing in elderly, healthy subjects is linear and accumulation is predictable. There were no obvious differences between the kinetics for our subjects compared with that for young adults (20). Age-related declines in renal function or possibly other factors and not age, per se, may account for the high concentrations in plasma and the toxicity observed in some elderly patients treated with the conventional dosage (200 mg/day) of rimantadine.…”

“…Thus, the small changes observed in the kinetic parameters across the age range in this study were (20). Only in time to Cmax did our study population differ from the younger adult population (2.5 and 1.9 h for the first and last doses, respectively, for our study population).…”

“…Despite their chemical similarities, rimantadine differs from amantadine in having lower concentrations in plasma, longer elimination half-life in plasma, and more complex metabolic disposition (1-3, 9, 10, 19). Previous studies (1,9,19,20) have characterized the single-dose kinetics of rimantadine in children and in both young and elderly adults, and their findings suggest that rimantadine pharmacokinetics in elderly, ambulatory adults do not differ substantially from those in younger adults and that dosage adjustments are unnecessary for older adults. However, several long-term prophylaxis studies with elderly nursing-home patients showed that rimantadine at the conventional dosage (200 mg/ day) is associated both with much higher concentrations in plasma than predicted by the earlier single-dose pharmacokinetic studies and with an excess of adverse reactions (13; R. Dolin After fasting overnight, the subjects reported to the Clinical Research Center where they received a 100-mg rimantadine tablet with 240 ml of water immediately prior to a standard breakfast.…”

In Vitro and In Vivo Activities of Aminoadamantane and Aminoalkylcyclohexane Derivatives againstTrypanosoma brucei

“…Pharmacokinetic data are not available for most of the compounds used in the study described in this report, but both amantadine and rimantadine have been well studied. Steady-state levels in serum of 0.5 to 1.0 g ml Ϫ1 (2.5 to 5.0 M) and above and serum half-lives of between 24 and 36 h have been widely reported (1,2,9,14,26). In addition, the drugs readily gain access to the central nervous system (22).…”

“…They are inexpensive, can be taken orally, produce few side effects (8), and readily cross the blood-brain barrier (22). In addition, their pharmacokinetics in humans have been extensively investigated (9,26); they are well absorbed from the gastrointestinal tract and have a plasma half-life of up to 36 h. The target of these drugs is the viral protein M2, which forms a tetrameric voltage-gated proton channel (17) and functions by translocating protons across the viral membrane into the viral core (5). This acidification process facilitates the release of viral RNA.…”