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Abstract

Prior to evaluating the effect of ranitidine on theophylline absorption from a sustained-release theophylline tablet, the effect of ranitidine on the time course of gastric pH in 12 healthy subjects was evaluated with an encapsulated radio-telemetry device (Heidelberg capsule). Gastric pH was measured hourly from 7 AM to 1 PM prior to beginning ranitidine treatment at 2 PM (150 mg every 4 hr for eight doses). The next day, pH was again measured hourly from 7 AM to 7 PM. Subjects fasted overnight and remained fasted until lunch at 11 AM. Prior to ranitidine treatment, the mean morning gastric pH remained between 1.5 and 2.2. After lunch, the pH increased to 2.2-2.3. During ranitidine treatment the mean morning gastric pH measurements were 5.5 to 5.8, decreasing after lunch to 3.1 by 4 PM and increasing to 3.9 at 7 PM. One week later the subjects participated in a three-way crossover theophylline bioavailability study receiving at weekly intervals, single doses at 7 AM of (a) 5 x 100-mg immediate-release tablets, (b) 2 x 300-mg sustained-release theophylline tablets, and (c) 2 x 300-mg sustained-release theophylline tablets after ranitidine pretreatment of 150 mg every 4 hr beginning at 2 PM the previous day. The increase in gastric pH with ranitidine had no effect (P greater than 0.05) on the rate and extent of absorption or on the elimination rate of theophylline.

Synthesis of novel aromatic macrolactones via ring closing metathesis of substituted phenylalkanoic acid allylic esters

“…Indeed, Furstner and Langerman were the first to demonstrate that unsaturated esters could be cyclized by Ring Closing Metathesis (RCM) to the macrolactones, showing essentially that the RCM approach compares favorably with other macrocyclization methods, Scheme 1. In a reported study, RCM reactions on dienes of the type shown in Scheme 2 have yielded macrocyclic "headto-tail" dimers and trimers [15]. This discovery was subsequently applied by Grubbs in the synthesis of the antifungal antibacterial natural product (-)-pyrenophorin.…”

“…Among the established macrocylization approaches is the macrolactonization protocol [15][16][17][18][19], that has been employed in the synthesis of a wide variety of macromolecules of high significance. A more recent protocol employs olefin metathesis chemistry mediated by one of the reported metathesis catalysts.…”

A Novel In Situ Gel Formulation of Ranitidine for Oral Sustained Delivery

“…A conventional dose of 150 mg can inhibit gastric acid secretion up to 5 hours but not up to 10 hours. An alternative dose of 300 mg lead to plasma fluctuations; thus a sustained release dosage form of ranitidine was desirable (Betlach et al ., 1991). Moreover, due to the short biological half-life of drug (∼2.5–3 hours), and consequently, a frequent dosing regimen was needed.…”