Pharmacy & Therapeutics - March 2009 - (Page 149) PPIs in Enteral Nutrition pH above 4 correlated well with the mean pH for all 22 patients (r = 0.84). Dunn et al.17 As seen in these studies, concerns remain about the administration of capsule contents and the premature activation of the PPI molecule, particularly when patients are compromised by delayed gastric emptying and by limitations to the use of sodium bicarbonate as a protective agent. Therefore, the vehicle in which the granules are administered is of equal importance. Dunn and colleagues sought to determine whether omeprazole differed from lansoprazole in the number of granules delivered and whether water or apple juice served as a better vehicle of delivery. The investigators chose apple juice as a delivery medium because it was recommended by lansoprazole’s manufacturer and because some studies indicated that acidic fruit juices would maintain the composition of omeprazole for up to 30 minutes. This in vitro study also compared how well 15 mL, compared with 30 mL, of the liquid vehicle delivered the medication granules. The investigators individually counted the contents of each capsule and then mixed them with either 30 mL of water or with 15 mL of water or apple juice. A nasogastric tube was placed in a position similar to what it would be in a supine patient. The medication was administered through the tube and collected by a filter at the end. Two investigators recounted the granules. Approximately 50% of omeprazole granules and approximately 30% of the lansoprazole granules were delivered; this result was not found to be statistically significant (P > 0.05). However, when counts exceeding a 95% delivery were excluded, delivery rates did differ significantly between the two medications (approximately 45% for omeprazole vs. approximately 15% for lansoprazole; P = 0.01). Delivery rates were not affected by the amount or type of vehicle used. prazole granules. Significant differences were found between several pharmacokinetic parameters (Tmax, Cmax, and AUC); however, the Cmax and AUC point estimates fell within the 90% CIs that determined bioequivalence (1.136, 90% CI, 1.037– 1.244, and 0.851, 90% CI, 0.806–0.898, respectively). Because the capsule and suspension formulations were found to be bioequivalent, the differences noted in individual parameters are likely to be of limited clinical significance. Freston et al.20 Freston et al. completed a comparative study of lansoprazole dispersion in apple juice given via nasogastric tube with IV pantoprazole. This crossover study compared pharmacokinetic and intragastric pH on the first and fifth days of treatment. This trial again demonstrated that the bioavailability of lansoprazole was not affected when it was given in an alternative form. On the first day of treatment, patients receiving lansoprazole had a significantly higher mean pH than those treated with pantoprazole at 0 to 5 hours (P = 0.0.29), at 6 to 10 hours (P = 0.001), and at 11 to 15 hours (P = 0.016). The percentage of time spent above a pH of 3, 4, and 5 was also significantly higher in the lansoprazole group (P < 0.001 for all). On day five of treatment, only the mean pH at the 6- to 10hour segment and the 11- to 15-hour segment remained significantly higher for lansoprazole (P = 0.004 and P = 0.048, respectively). As for the percentage of time spent at a determined pH, only a pH above 3 for patients treated with lansoprazole remained significant (P < 0.05). The authors pointed out several limiting factors that apply to all of the studies described thus far. Each study involved healthy, primarily male patients. From the literature, it is difficult to determine whether bioavailability and efficacy would remain the same in different patient populations. Freston et al. mentioned that PPIs were administered only once daily and that the effects on pH might be different with an increased frequency. Olsen and Devlin21; Tsai et al.22 Lansoprazole Chun et al.18 As demonstrated in the in vitro study by Dunn et al., the administration of lansoprazole granules via nasogastric tube resulted in a very low delivery rate.17 However, a small study by Chun et al. estimated that the number of granules that adhered to tubing was minimal (2% or less). In this crossover study, 23 healthy male volunteers were given an intact lansoprazole capsule and lansoprazole granules in apple juice. The primary objective was to determine differences in bioavailability. After evaluating pharmacokinetic parameters, the authors noted no significant difference between the capsule and granule formulations in their times to maximum concentration (Tmax), peak concentration (Cmax), half-life, or AUC concentration. The AUC point estimate fell within the 90% confidence interval (CI), indicating that the two formulations were bioequivalent (1.044, 90% CI, 0.955–1.140). Doan et al.19 A second study of 36 healthy volunteers revealed similar results. The Doan study also had a crossover design, but a sodium bicarbonate suspension was used to deliver the lanso- Two trials have demonstrated the efficacy of nasogastric administration in critically ill patients.21,22 Olsen and Devlin administered lansoprazole orally disintegrating tablets, according to package insert instructions, and compared them with IV lansoprazole. They found that the bioavailability of enterally administered lansoprazole was lower than that of the IV formulation, but its acid-suppressing ability was greater.21 Another study involving 15 critically ill patients documented similar results. Tsai et al. evaluated gastric pH and the percentage of time spent above a pH of 4 when lansoprazole granules were administered in water.22 The median pH was significantly higher on the second and third days (P = 0.001), and the percentage of time spent above a pH of 4 was significantly higher on these days when compared with baseline values (76% and 84%, respectively, P = 0.001).22 Because water was used as the delivery medium, a concern was raised about exposure of the lansoprazole granules to stomach acid with a resulting premature activation of the drug. The Tsai study potentially circumvented this event by Vol. 34 No. 3 • March 2009 • P&T® 149
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