Pantoprazole dosage

Pantoprazole sodium, in its bulk drug form or in tablet dosage forms, can be directly determined on the basis of its direct ultraviolet absorbance after being dissolved in 0.1 M NaOH. 

The area under the curve of pantoprazole plasma concentration versus time (AUC) for a slow metabolizer is generally approximately 5 times higher than that for an average patient. Since pantoprazole is considered safe and well tolerated, and no dosage related adverse drug reactions have been identified, this finding seems to be of no clinical relevance. 

Omeprazole (p. 171) can cause maximal inhibition of HC1 secretion. Given orally in gastric juice-resistant capsules, it reaches parietal cells via the blood. In the acidic milieu of the mucosa, an active metabolite is formed and binds covalently to the ATP-driven proton pump (H+/K+-ATPase) that transports H+ in exchange for I<+ into the gastric juice. Lansoprazole, pantoprazole, and rabeprazole produce analogous effects. Omeprazole is a racemate. With respect to dosage, the now available (S)-omeprazole (esomeprazole) represents the more potent enantiomer, but this offers no therapeutic advantage. 

Information is limited, but what is eurrentiy known suggests that patients given omeprazole, and possibly esomeprazole, with diazepam may expe-rienee inereased benzodiazepine effeets (sedation, unstable gait ete). If this oeeurs the benzodiazepine dosage should be reduced. Lansoprazole, pantoprazole and rabeprazole do not appear to interaet with diazepam. 

A 69-year-old woman developed confusion and paranoia over several days. She was taking carvedilol 12 mg bd, warfarin 2 mg/day, folic add 1 mg/day, levothyroxine 100 micro-grams/day, pantoprazole 40 mg/day, paroxetine 40 mg/day, and flecainide 100 mg bd. The flecainide had been started 2 weeks before. The plasma flecainide concentration was 1.36 mg/1. Paroxetine was withdrawn and the dosage of flecainide was reduced to 50 mg bd. Her delirium resolved 3 days later. 

As opposed to lansoprazole and pantoprazole, hepatic metabolism seems to saturate at higher dosages of omeprazole (40 mg) [13]. Although dose linearity is a desirable feature, its advantages may be elusive since PPIs show considerable interindividual variation in bioavailability [14, 15]. 

Figure 1. Effective loads of PPIs used at standard dosages. Molar loads depend on dose and bioavailability and, according to elimination rates, translate into different values of AUC. Ome, omeprazole lanso, lansoprazole panto, pantoprazole.

At standard dosages, plasma elimination of omeprazole is fastest. Excretion occurs, to different proportions, by renal and faecal routes (Tab. 1). Omeprazole metabolism seems to be saturable, so that 40-mg doses of omeprazole and pantoprazole are excreted at the same rates (1.25 h) [22]. 

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