Robert C. Lanman

Effect of food coadministration on 5-aminosalicylic acid oral suspension bioavailability.

Single doses of 1 gm 5‐aminosalicylic acid (5‐ASA) suspension was administered to 24 healthy volunteers during both fasting and fed conditions. For subjects in a fasting state, plasma 5‐ASA and acetyl 5‐ASA concentrations peaked rapidly 1 hour after dosing to 14.72 μg/ml and 11.4 μg/ml, respectively. The elimination half‐life of 5‐ASA was 51.9 minutes, whereas the acetyl 5‐ASA half‐life could not be determined. A mean of 78.3% of the dose was excreted in the urine, with 5‐ASA accounting for 21.2% of the dose and acetyl 5‐ASA accounting for the balance. Only 11.3% of the dose was eliminated in the feces, consisting mostly of acetyl 5‐ASA. Food coadministration reduced 5‐ASA and acetyl 5‐ASA systemic relative bioavailability to 44% and 76%, respectively, compared with the fasting treatment. Urinary excretion of the salicylates was reduced to 46.8%, and fecal salicylate elimination increased almost 100%– to 24.2% of the total dose.

Diffusion coefficients of some 14C-labeled saccharides of biological interest

Abstract Coefficients of free diffusion of some 14 C-labeled saccharides in saline were determined at 37°C by the agar gel method of Schantz and Lauffer. The following values (× 10 −6 cm 2 /sec) were obtained: [1- 14 C]D-mannitol, 9.16; [U- 14 C]D-sucrose, 6.99; [ 14 C] carboxyinulin, 2.98; [ 14 C] hydroxymethyl-inulin, 2.49; and [ 14 C] carboxydextran (mol wt range 60, 000–90, 000), 1.33. The coefficients for 14 C-labeled mannitol, sucrose, and carboxy-inulin were in reasonably close agreement with previously reported literature values and with Stokes-Einstein calculated coefficients. The value for [ 14 C] hydroxymethyl-inulin differed from that of [ 14 C] carboxy-inulin, but was similar to previously reported values for native (unlabeled) inulin. The measured diffusion coefficient for [ 14 C] carboxydextran was somewhat greater than the coefficient calculated from the Stokes-Einstein equation for a compound with an average molt wt of 75, 000.

Pharmacokinetics of 5-aminosalicylic acid from controlled-release capsules in man

One gram single dose of Pentasa controlled-release capsules was administered to 24 healthy volunteers under fasting condition. Mean plasma 5-aminosalicylic acid (5-ASA) and acetyl 5-ASA concentrations peaked at 0.53 μg · ml−1 and 1.33 μg · ml−1 from 3 to 4 hours following dosing, respectively. The half-lives of both compounds could not be determined as absorption of 5-ASA was continuous throughout the gastrointestinal tract. An average of 29.4% (CV: 27%) of the dose was excreted in the urine primarily as acetyl 5-ASA. Up to 91.1% of the dose was released from the capsules. Forty percent of the dose (CV: 40%) was eliminated in the feces, with 8.9% of the dose remained as formulation bounded 5-ASA, indicating that controlled-release capsules continue to release drug throughout the GI tract. 5-ASA contributed 46.7% of the salicylates eliminated in the feces and acetyl 5-ASA accounted for the balance. Controlled-release capsules produced three times more total salicylates and 10 times more total and free 5-ASA in the feces than did 5-ASA suspension. Thus, while lower systemic levels of salicylates were absorbed, greater therapeutic quantities of 5-ASA were available in the bowel.

Absorption of Organic Anions from the Rat Small Intestine

Abstract1. Hippuric acid, sulphanilic acid, p-aminohippuric acid, and phenol red, highly ionized compounds of very low lipoid solubilities, were absorbed from the rat small intestine at rates which varied over a 25-fold range.2. Absorption rates ranked in the same order as the chloroform-to-water partition coefficients of the compounds but not in the order of the molecular weights or degrees of ionization.3. The results suggested that these anions are absorbed mainly by simple diffusion through lipoid regions of the intestinal boundary.

Bioavailability of theophylline following a rectally administered concentrated aminophylline solution

A two-way complete crossover bioavailability study of solutions of theophylline given orally or rectally in 16 healthy subjects was conducted. Blood samples were obtained prior to dosing and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2,5, 3, 3,5, 4, 4.5, 5, 6, 7, 8, 10, 12, and 24 hr. Plasma theophylline was determined by high-pressure liquid chromatography. In the fasting subjects solutions given orally were absorbed faster (0.95 versus 1.95 hr to peak), reaching a higher peak concentration (7.26 versus 4.87 microgram/ml) than the solutions given rectally. Depending on the method of computation, solutions given rectally were estimated to be 86% to 87% as biovailable as the solutions given orally, with 75% of the subjects having 80% or greater relative bioavailability.

High Pressure Liquid Chromatographic Determination Of Dextrorphan In Human Plasma

Abstract A method is presented for determination of dextrorohan, the O-demethylated metabolite of dextromethorphan, in human Dlasma. Following enzymatic hydrolysis of the glucuronide conjugate, extraction and back extraction prepare the sample for resolution by reverse-phase high pressure liquid chromatography with fluorescence detection. The method is sensitive, specific, precise and reproducible.

Determination of Propranolol and Three Metabolites in Rat Bile by Gradient Elution HPLC

Abstract A gradient elution HPLC method for analysis of propranolol and three basic metabolites in bile is presented. Before or after hydrolysis with beta-glucuronidase, acetonitrile is added to the bile sample, the resulting mixture is centrifuged at high speed, a portion of the supernatant is diluted with buffer and an aliquot is injected onto the HPLC column. The method utilizes gradient elution, reverse phase chromatography with fluorescence detection, and is sufficiently sensitive to quantitate 1.25 mcg/ml of compound using 50 μl to 100 μl of bile sample.