Omeprazole induces gastric permeability to digoxin.

Previous animal and patient-based studies have shown that omeprazole induces a transepithelial paracellular gastric leak. This study reports on the potential for an omeprazole-induced leak of drugs with narrow therapeutic windows. Ussing chamber experiments investigated the effects of omeprazole on rat gastric corpus permeability to the drugs, digoxin and phenytoin. Digoxin (780 MW) permeated the gastric mucosa at an accelerated rate in the presence of omeprazole. This leak could contribute to dangerous elevations of blood digoxin levels in certain situations. Omeprazole was found to have no effect on the flux rate of phenytoin (252 MW). The tight-junctional leak generated by omeprazole thus exhibits specificity to the types of molecules it allows to permeate through the gastric mucosa. This leak may pose a clinical danger by increasing drug uptake into the bloodstream, a phenomenon which would act synergistically with the effect of omeprazole on inhibiting liver cytochrome P450s that remove drugs from the bloodstream, thereby elevating drug blood levels.

Acute effects of parathyroid hormone on proximal bicarbonate transport in the dog.

Re-collection micropuncture and simultaneous clearance studies were performed in thyroparathyroidectomized (TPTX) dogs to evaluate the effects of the acute administration of parathyroid hormone (PTH) on bicarbonate reabsorption. The i.v. administration of PTH from 74 to 94 U/hr reduced proximal fractional reabsorption (FRHCO3) from 0.28 +/- 0.03 to 0.14 +/- 0.03 (P less than 0.005) and absolute bicarbonate reabsorption (THCO3) from 556 +/- 126 to 255 +/- 73 pmoles/min (P less than 0.05), whereas there were no changes in PCO2 (37.0 +/- 1.4 leads to 37.2 +/- 1.4 mm Hg, P greater than 0.90), plasma bicarbonate (PHCO3) (18.5 +/- 0.4 leads to 18.3 +/- 0.4, P less than 0.60), single nephron glomerular filtration rate (102.2 +/- 15;9 leads to 90.1 +/- 10.3 nl/min, P greater than 0.40), serum ultrafilterable phosphate concentration (SUFp) (1.71 +/- 0.13 leads to 1.83 +/- 0.12 mmoles/liter, P greater than 0.25), or serum ultrafilterable calcium (SUFCa) (1.85 +/- 0.05 leads to 1.88 +/- 0.05 mEq/liter, P greater than 0.60). PTH also reduced proximal fractional fluid (and sodium) reabsorption (0.40 +/- 0.04 leads to 0.28 +/- 0.08, P less than 0.05) while TFHCO3 did not change (20.5 +/- 0.4 leads to 20.8 +/- 0.4 mmoles/liter) indicating a rejection of bicarbonate proportional to the inhibition in tubular fluid transport. The invariable reduction in proximal bicarbonate reabsorption did not uniformly result in an increased urinary bicarbonate concentration.