[Pharmacokinetics of PF-402, sustained-release morphine capsule, in cancer patients with pain].

A once-daily dose of PF-402 60 mg and twice-daily doses of sustained-release morphine sulfate tablets (MSC) 30 mg were repeatedly administered in cancer patients in a cross-over design. Their plasma concentrations were measured, and the pharmacokinetics of PF-402 and MSC were compared. A total of 7 subjects in the study were taking commercially sold MSC 60 mg daily (30 mg twice-daily) prior to the study and had "mild" or "no" pain at the start of the study. Plasma morphine concentrations of PF-402 were longer-lasting and showed smaller fluctuations than those of MSC. Repeated administration of the same daily doses of PF-402 and MSC produced similar plasma concentrations for periods of 24 hr and 12 hr. PF-402 administration produced a Tmax of 7.4 hr, and an MRT of 9.8 hr, all longer than those with MSC. Moreover, no significant difference was observed in AUC between PF-402 and MSC. These results indicate that the sustained-release characteristics of PF-402 are superior to those of MSC, and that the two drugs have a similar absorption pattern. Adverse drug reactions (ADRs) were observed in all 7 subjects and consisted of 6 incidences of constipation, 3 incidences of nausea, 2 incidences of itching, and 1 incidence each of vomiting and somnolence. Study drug administration was not discontinued in any case due to ADRs, and no symptoms indicating physical or psychic drug dependence were observed. No abnormal laboratory values related to study drug administration were observed. The above results indicate that once-daily administration of PF-402 is sufficient to maintain plasma concentrations obtained with twice-daily administration of MSC. As the safety of PF-402 is confirmed, the drug is considered to be a useful sustained release formulation in the treatment of cancer pain.