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Rabeprazole, a newly developed proton pump inhibitor, has been shown to be effective for the treatment of gastric and duodenal ulcers and for gastro-oesophageal reflux disease. It is a rapid and potent inhibitor of gastric H+,K(+)-ATPase, the gastric acid (proton) pump. The maximum plasma concentration (Cmax) and the area under the plasma concentration time curve (AUC) are linearly related to dose, while the time to maximum plasma concentration (tmax) and elimination half-life (t1/2) are dose-independent. Rabeprazole is extensively metabolized in the liver via the cytochrome P450 enzyme system, and its metabolites are excreted primarily in the urine. Rabeprazole does not accumulate with repeated dosing. Its bioavailability is not influenced by the coingestion of either food or antacids. The pharmacokinetic profile of rabeprazole is substantially altered in the elderly and patients with stable compensated chronic cirrhosis; however, these alterations are not associated with clinically significant abnormalities in laboratory parameters or serious adverse events. The influence of severe decompensated liver disease on the pharmacokinetics of rabeprazole has not been assessed. The pharmacokinetic profile of rabeprazole is not significantly altered by renal dysfunction requiring maintenance haemodialysis. These findings suggest that dosage adjustment is not required in these special patient populations. Caution should be exercised, however, in patients with severe liver disease.

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Patients with acid-related diseases often need to take multiple medications. Treatment of Helicobacter pylori infection often includes either a histamine type 2 (H2)-receptor antagonist or a proton pump (H+,K(+)-ATPase) inhibitor (proton pump inhibitor), administered in conjunction with one or more antimicrobials. Also, treatment for acid-related diseases often requires extended therapy during which many concomitant medications may be administered for concurrent disease states. Polypharmacy may be the result, particularly in elderly patients, who are at increased risk for both acid-related and many other diseases. Thus, it is important to understand the potential for clinically significant drug-drug interactions in this setting. H2-receptor antagonists and proton pump inhibitors can influence the pharmacokinetic profiles of other commonly administered medications by elevating intragastric pH, which can alter drug absorption, and by interacting with the cytochrome P (CYP) 450 enzyme system, which can affect drug metabolism and clearance. Such interactions are particularly important when they affect the pharmacokinetics of drugs with narrow therapeutic ranges (e.g. warfarin, digoxin). In these cases, drug-drug interactions can result in significant toxicity and even death. There are marked differences among H2-receptor antagonists and proton pump inhibitors in their potential for such interactions. The oldest drugs in each class, cimetidine and omeprazole, respectively, have the greatest potential to alter CYP activity and change the pharmacokinetics of other drugs. The most recently developed H2-receptor antagonist, famotidine, and the newer proton pump inhibitors, rabeprazole and pantoprazole, are much less likely to induce or inhibit CYP and thereby change the metabolism of other medications. These differences are important when choosing medications for the safe treatment of patients with acid-related diseases.

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STUDY OBJECTIVE: To determine the single-dose pharmacokinetics of gentamicin in healthy humans undergoing hyperbaric oxygen (HBO) exposure. DESIGN: Randomized, crossover trial. SETTING: Specialized hyperbaric research facility within a United States Air Force medical center. SUBJECTS: Five healthy men between 28 and 43 years of age. INTERVENTIONS: Each subject received a total of two doses of intravenous gentamicin 1.5 mg/kg lean body weight spaced at least 2 weeks apart. One dose was infused under normobaric oxygen (NBO) conditions and the other under HBO conditions. MEASUREMENTS AND MAIN RESULTS: Gentamicin pharmacokinetic values were determined on 11 serum samples per subject collected sequentially out to 300 minutes after infusion. Using PCNONLIN, the following results demonstrated no difference between the pharmacokinetic values under HBO and NBO conditions, respectively: beta half-life (112, 115 min); volume of distribution (0.201, 0.184 L/kg); peak concentration (6.52, 7.23 mg/L); clearance (0.0754, 0.0676 L/kg/hr). CONCLUSIONS: Hyperbaric oxygen produced no changes in the measured pharmacokinetic values of gentamicin under the conditions specified in this study. It is possible that numerous HBO exposures could produce a cumulative effect on gentamicin pharmacokinetics that would not be discernible in a single-dose study. Because of the profound physiologic effects of HBO, drugs with narrow therapeutic indexes should be evaluated under HBO conditions if they are to be given to patients receiving HBO treatments.

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We developed algorithms for confirmation and identification of benzodiazepines and their metabolites, initially detected in urine samples by enzyme-multiplied immunoassay (EMIT). These algorithms are based on the pattern of benzophenone derivatives of benzodiazepines obtained by gas chromatography-mass spectrometry (GC-MS) with use of a modified specific ion selection mode. Benzophenone derivatives were produced by acid hydrolysis of urine samples containing benzodiazepines and (or) their metabolites. We present mass spectra of the newer benzodiazepines--alprazolam, midazolam, and triazolam--and we determined the detection limit (0.2 mg/L) for these drugs as measured with the EMIT d.a.u. benzodiazepine assay and the ETS instrument (both from Syva Co.). We conclude that these algorithms are useful mostly in forensic toxicology in which unequivocal identification of benzodiazepines is the desired goal.

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Serum drug concentration data from the first of the two patients described herein suggest that rifampin may directly increase the metabolism of quinidine and thereby negate the influence of quinidine on the serum digoxin concentration (SDC). Data on the second patient suggest that rifampin may directly increase the metabolism of digoxin producing lower SDC values. In both cases, the discontinuation of rifampin therapy appears to have allowed reversion toward prerifampin metabolism of both quinidine and digoxin.

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A case of an adverse reaction occurring in a 53-year-old, aspirin-sensitive asthmatic male with nasal polyps following administration of a 400-mg ibuprofen tablet is reported. Symptoms of the adverse reaction included an urticarial rash, labored breathing, laryngeal edema and tightness of the chest. Treatment consisted of isoproterenol inhalant (self-administered), subcutaneous epinephrine 0.25 mg, intramuscular diphenhydramine hydrochloride 50 mg and intravenous hydrocortisone 250 mg. The pathogenesis of the patient's adverse reaction and the possible fole of aspirin, of other analgesics and of tartrazine in its development are discussed. The adverse reaction was not mediated immunologically but rather resulted from the prostaglandin synthetase (PGS)-inhibitor activity shared by aspirin, ibuprofen and other analgesics. Selection of an analgesic for an aspirin-sensitive patient should be based on the analgesic's PGS-inhibitor activity.

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The operation of a drug information center (DIC) was studied after it was relocated from a school of pharmacy to a teaching hospital. The output during the last eight months in the school of pharmacy (Period 1) was compared to the output during a three-month period after the DIC became established in the hospital (Period 2). Questions were classified by type and profession or requester. In addition, the number of judgmental questions processed was determined. The average number of questions per month in Period 1 was 58.1, while during Period 2 it was 146.3. There was a statistically significant increase in Period 2 in questions from each profession, with the exception of clinical pharmacists. In Period 2, 30.8% of the questions were asked by physicians, 27.6% by pharmacists, 24.1% by clinical pharmacists, 12.3% by nurses and 5.2% by other professionals. The largest number of questions was in the pharmacological category, with toxicities or side effects as the largest class. The majority of questions asked by nurses were pharmaceutical. Of the 439 questions received during Period 2, 28.0% were judgmental. Pharmaceutical questions were found to require the least amount of time to answer, while therapeutic questions required the greatest amount of time. Judgmental questions required more time than nonjudgmental questions. It was concluded that increased visibility and accessibility of the DIC after its relocation resulted in an increased work load.

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