C. Alioth et al., APPLICATION OF DUAL RADIOTELEMETRIC TECHNIQUE IN STUDYING DRUG-DRUG INTERACTION BETWEEN DICLOFENAC SODIUM AND RANITIDINE HCL IN VOLUNTEERS, Pharmaceutical research, 10(11), 1993, pp. 1688-1692
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.