The dissolution and oral bioavailability of mexiletine capsules modified for clinical trial. A preliminary report.
The dissolution and bioavailability of two preparations of mexiletine hydrochloride (200 mg), one available commercially as Mexitil and one modified by the Hospital Pharmacy for a clinical trial, were investigated in a cross-over study with healthy volunteer subjects. The evaluation of bioavailability was based on comparisons of the mean residence time (MRTp.o.) and mean absorption time (MATp.o.), areas under the plasma mexiletine concentration time-curve (AUC) and urinary recovery of unchanged mexiletine under controlled condition of acidic urinary pH after oral administration of single doses of either 400 mg or 200 mg as mexiletine hydrochloride. Three different methods of calculation were used to account for possible changes in clearance of the drug in between treatments. Bioavailability data were available from 3 cross-over studies as the investigation was terminated because one subject experienced idiosyncratic reactions to mexiletine. The mean-transit-time, T DISSOLVED-IN VITRO, for the hospital-modified capsules (2.8 min) was longer than that of the Mexitil capsule (2.0 min) in 0.1 HCl. This delay in dissolution was complemented by an increase in MATp.o. (0.43 and 0.58 hr respectively for Mexitil and hospital-modified capsules) obtained in one subject. The bioavailabilities of the two preparations were comparable from AUC between 0 to 6 hr, but the plasma curves from 6 to 48 hr were not followed. The mean times in vivo, T MEAN-IN VIVO (determined from urinary elimination curves in a cross-over study of 3 subjects) were consistently shorter after ingestion of Mexitil capsules though the significance was difficult to obtain due to small sample size.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D001682:Biological Availability; D002214:Capsules; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008801:Mexiletine / Q000008:administration & dosage* / Q000378:metabolism; D008954:Models, Biological; D011437:Propylamines / Q000008:administration & dosage*; D012995:Solubility
D002214:Capsules; D011437:Propylamines; D008801:Mexiletine