Comparative bioavailability characteristics of commercial quinidine polygalacturonate and sulfate tablets.

This study compared the relative bioavailability characteristics of quinidine polygalacturonate (QP) and quinidine sulfate (QS) after oral administration of commercial tablets and a liquid form prepared from crushed tablets in 13 healthy adult male volunteers. Each subject received the following four single-dose treatments in a randomized, crossover manner with a one-week washout period between treatments: 400 mg QS liquid, two 200-mg QS tablets, 550 mg QP liquid, and two 275-mg QP tablets. All four treatments were equivalent in terms of the dose of quinidine base. Multiple serum samples and two 24-hour urine specimens were collected over 24 and 48 hours, respectively, and assayed for quinidine with a specific HPLC assay method. For the absorption and disposition parameters measured (maximum serum concentration, time to reach maximum concentration, area under the concentration-time curve [0-48 hours], absorption and elimination rate constants, absorption and elimination half-lives, apparent total body clearance, apparent volume of distribution, and dose fraction excreted in the urine) no significant differences were observed for any of the parameters among the four treatments (p greater than 0.05). The results of the present investigation demonstrated that QP and QS produced identical serum quinidine concentration-time curves when given in the form of a tablet or liquid. The clinical implications of these observations with respect to the dosing of QP are discussed.

Compatibility of lithium citrate syrup with 10 neuroleptic solutions.

The visual compatibility of lithium citrate syrup (1.6 meq Li+/ml) in mixtures with each of 10 neuroleptic drug solutions or concentrates was studied. Lithium citrate syrup (5 or 10 ml) was mixed with four volumes (representing minimal to maximal clinical dosages) of each of 10 liquid neuroleptic drug products--chlorpromazine hydrochloride, haloperidol lactate, thioridazine hydrochloride, trifluoperazine hydrochloride, fluphenazine hydrochloride, loxapine hydrochloride, mesoridazine besylate, molindone hydrochloride, perphenazine, and thiothixene hydrochloride. Samples were prepared in duplicate by both orders of mixing at 25 +/- 2 degrees C and 4 +/- 1 degrees C and observed visually immediately and six hours later. Samples observed to be incompatible were centrifuged, and resulting layers were tested for drug with thin-layer chromatography. At six hours after mixing, pH values of the mixtures were measured. Chlorpromazine, haloperidol, thioridazine, and trifluoperazine products were incompatible with lithium citrate syrup; other products were compatible. Centrifugation of incompatible mixtures yielded two liquid phases--a more voluminous clear supernatant and a viscous, translucent, hydrophobic sediment. Thin-layer chromatography verified the presence of the neuroleptic drug in both phases. The incompatibility is independent of pH and lithium or citrate ions. The four incompatible neuroleptic solutions were each mixed with 1.64 M sodium chloride solution, and the same incompatibility was noted as with 5 ml of lithium citrate syrup. This suggested that the precipitation is caused by excessive ionic strength in the mixtures, resulting in salting out of undissociated, solvated ion pairs of the protonated neuroleptic bases and their respective anions. The incompatible mixtures should be avoided because clinically important underdoses could occur.