APPLICATION OF DUAL RADIOTELEMETRIC TECHNIQUE IN STUDYING DRUG-DRUG INTERACTION BETWEEN DICLOFENAC SODIUM AND RANITIDINE HCL IN VOLUNTEERS

Drug-drug interaction between a commercial diclofenac sodium enteric-c oated tablet (Voltaren; V) and a ranitidine HCl tablet (Zantac; Z) was evaluated using a dual radiotelemetric technique according to a rando mized three-way Latin-Square crossover design balanced for carryover e ffects. V and Z were given either alone or in combination (Treatment V , Z, V/Z), with a 14-day washout period between treatments. Eighteen f asted subjects swallowed a tethered Heidelberg pH capsule to provide c ontinuous gastric pH. Then the assigned treatment drug and another Hei delberg pH capsule were given simultaneously. The free pH capsule prov ided information regarding gastric residence time (GRT). Serial blood samples were obtained for up to 12 hr after dosing and drug levels wer e determined by validated HPLC methods. Treatment effects on AUC, C(ma x), T(max), T(lag), T(max)-T(lag), and T1/2 were not significant excep t C(max), which differed slightly for both V and Z when given in combi nation as compared to alone. Gastric residence times were 46, 33, and 51 min for Treatments V, Z, and V/Z, respectively. Gastric exposure of the enteric-coated tablet of diclofenac was estimated by pH values ob tained from the tethered capsule. Median pH values at 3 and 15 min pri or to gastric emptying were 3.8 and 4.9 for the combination treatment versus 2.1 and 2.7 for diclofenac alone. The results of this study ind icated that there was minimal drug-drug interaction between diclofenac and ranitidine. The gastric pH range resulting from this study did no t influence the oral absorption of enteric-coated diclofenac.