PH-RELATED CHANGES IN THE ABSORPTION OF DIPYRIDAMOLE IN THE ELDERLY

The bioavailability of dipyridamole, a poorly soluble weak base, was e valuated in 11 healthy, older subjects (greater-than-or-equal-to 65 ye ars), 6 with a low fasting gastric pH (control) and 5 with a fasting g astric pH > 5 (achlorhydric), in a randomized, crossover design. Subje cts received 50 mg dipyridamole as a single oral dose both with and wi thout pretreatment with 40 mg famotidine (control subjects) or 1360 mg glutamic acid HCl (achlorhydric subjects). Gastric pH was monitored b y Heidelberg radiotelemetric capsule. Gastric emptying of Tc-99m-radio labeled orange juice was measured. Gastric pH appeared to be a primary determinant in dipyridamole absorption in the elderly. Elevated gastr ic pH resulted in compromised dipyridamole absorption compared to low- gastric pH conditions in all cases. The administration of glutamic aci d hydrochloride to achlorhydric subjects prior to the dose of dipyrida mole corrected for the decreased C(max) and AUC(0-36) exhibited in ach lorhydric subjects without pretreatment. T(max) and k(a) were slower i n achlorhydrics, although pretreatment with glutamic acid HCl tended t o normalize these parameters. Based on these results, it would be bene ficial for achlorhydrics to take glutamic acid hydrochloride prior to taking dipyridamole and other medications which need a low gastric pH for complete absorption. The administration of 40 mg famotidine was su ccessful in elevating the gastric pH to >5 in all subjects and maintai ned it at >5 for at least 3 hr in all subjects tested. The lack of dif ferences in C(max) and AUC(0-36) with significant differences in T(max ) and k(a) indicated that control subjects after treatment with famoti dine may serve as an adequate model for achlorhydrics with respect to the extent of absorption, but not with respect to the rate of absorpti on. Gastric emptying of a nutrient liquid was significantly slower in achlorhydfic subjects than in control subjects. Finally, fasting serum gastrin appeared to be a relatively reliable and easy method for scre ening for achlorhydria in the elderly.