Understanding the pharmacodynamics of the PPIs is more relevant than knowing their pharmacokinetic parameters, since the duration of action depends on the rate of de novo proton-pump regeneration, not the duration of drug circulating in the body. Although the mean plasma half-life (t 1/2) after a single 40-mg intravenous dose of pantoprazole is 1.0 hour (range, 0.8 to 1.3 hours), a steady state of acid secretion does not occur until after approximately three days of once-daily dosing because a balance develops between synthesis of new enzyme and drug inhibition of existing ATPase. Pantoprazole is acid unstable and is thus prepared as an enteric-coated tablet, which should not be crushed. Its absorption is rapid, and the maximum concentration occurs approximately 2.5 hours after single or multiple oral 40- mg doses. Pantoprazole is well absorbed, undergoes limited first-pass metabolism, and has an absolute bio-availability of approximately 77%. The drug may be taken without regard to meals or antacids. Its apparent volume of distribution (V) is approximately 11.0 to 23.6 L, and the serum protein binding is ~98%. Pantoprazole is extensively metabolized in the liver through the cytochrome P-450 system, predominantly by CYP2C19 demethylation with subsequent sulfation and has a serum elimination half-life of about 1.1 hours. Pantoprazole does not accumulate, and its pharmacokinetics are not altered by multiple daily dosing. No dose adjustments are recommended in geriatric patients or those with renal failure or mild to moderate hepatic failure. In patients with severe liver cirrhosis, the half-life is somewhat prolonged to seven to nine hours. Pharmacokinetic data for individuals under 18 are not available.
A pharmacokinetic trial evaluating single intravenous doses in healthy volunteers found that 20- mg, 40-mg, and 80-mg doses exhibited a linear relationship in regard to the primary pharmacokinetic characteristics of area under the curve and maximum concentration. The t 1/2, clearance, and V were consistently not influenced by different doses and were similar to the pharmacokinetic parameters noted earlier for oral administration.
A clinical trial in healthy volunteers found equipotent inhibition of gastric acid secretion by equal doses of oral or intravenous pantoprazole. The primary parameter for the equivalence analysis was the percentage of time at which the intragastric pH was at least 4 or higher. The secondary parameter was the percentage of time at which the intragastric pH was at least 3 or higher. Clinical efficacy and pharmacodynamic equivalence of oral and intravenous 40-mg doses of pantoprazole have also been demonstrated in patients with erosive esophagitis.[7,8,9]
Am J Health Syst Pharm. 2001;58(11) © 2001 American Society of Health-System Pharmacists
Cite this: Pantoprazole - Medscape - Jun 01, 2001.