Kinetics, dynamics, and bioavailability of bumetanide in healthy subjects and patients with chronic renal failure

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109801/1/cptclpt1986112.pd

Comparative Evaluation of the Hemodynamic Effects of Oral Cimetidine, Ranitidine, and Famotidine as Determined by Echocardiography

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90052/1/j.1875-9114.1995.tb04349.x.pd

Effect of Intragastric pH on the Absorption of Oral Zinc Acetate and Zinc Oxide in Young Healthy Volunteers

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142255/1/jpen0393.pd

High viscosity hydroxypropylmethylcellulose reduces postprandial blood glucose concentrations in NIDDM patients

The ability of high viscosity hydroxypropylmethylcellulose (HPMC) to reduce postprandial glucose concentrations was assessed in patients with non-insulin-dependent diabetes (NIDDM) and healthy volunteers. The study design consisted of a two-way crossover, single-dose administration of 10 g prehydrated high viscosity HPMC, or placebo, with a standard carbohydrate-rich meal. In patients with NIDDM, HPMC reduced blood glucose concentrations at the 60-, 75-, 90-, 120- and 150-min sampling intervals, with an average reduction in the maximum postprandial blood glucose concentration, Cmax, of 24% (P Tmax, remained unchanged. The area under the blood concentration versus time plot, AUC0-6h, was reduced by an average of 15% (P Cmax, Tmax and AUC0-6h) were unchanged. These results suggest that alterations in the blood glucose profile are mediated by luminal events rather than by changes in hormonal response. In contrast to the NIDDM patients, neither the pharmacokinetic parameters nor the blood glucose concentrations at specific sampling times were significantly affected by the coadministration of HPMC in healthy volunteers. Overall, the results of this study suggest that HPMC may be a useful adjunct in the management of NIDDM.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30526/1/0000158.pd

Salicylsalicylic acid causes less gastroduodenal mucosal damage than enteric-coated aspirin

The gastroduodenal mucosal damage caused by aspirin and nonsteroidal antiinflammatory drugs is a common clinical problem. We compared two medications designed to diminish mucosal damage: enteric-coated aspirin and salicylsalicylic acid (salsalate). Ten healthy volunteers were randomized to receive either 1.5 g salsalate twice a day or 650 mg enteric-coated aspirin four times a day for six days and were then crossed over to the other drug after a one-week medication-free period. Endoscopic inspection of gastroduodenal mucosa was performed at entry and again after six days of drug therapy for each medicine. Mean serum salicylate concentrations taken before the morning drug dose were 11.2 mg/dl for enteric-coated aspirin and 18.1 mg/dl for salsalate. Only one of 10 subjects receiving salsalate developed mild (grade 1) mucosal damage while six of 10 receiving enteric-coated aspirin developed moderate to severe damage (grade 2–3) (P= 0.01 ). Symptoms were mild in both groups. We conclude that salsalate causes less gastroduodenal mucosal damage than enteric-coated aspirin .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44409/1/10620_2005_Article_BF01536056.pd

Stereoselective, competitive, and nonlinear plasma protein binding of ibuprofen enantiomers as determined in vivo in healthy subjects

The plasma protein binding and competitive inhibition parameters of R(−)- and S(+)-ibuprofen were determined in vivo in 12 healthy subjects. Subjects participated in a 4×4 Latin square design in which oral solutions of drug were administered as 300 mg R (−)-ibuprofen, 300 mg S (+)-ibuprofen, 300 mg R (−)-+300 mg S (+)-ibuprofen, and 300 mg R(−)-+600 mg S (+)-ibuprofen. Unlabeled ibuprofen enantiomers were quantitated using a stereospecific reversed-phase HPLC assay, and plasma protein binding experiments were performed using radiolabeled 14 C-enantiomers and an ultrafiltration method at 37C. At therapeutic drug concentrations, the protein binding of each enantiomer was greater than 99%. Furthermore, the binding of ibuprofen enantiomers was Stereoselective and mutually competitive, as well as nonlinear. The bound-free data were fitted to a model in which the non-linearity of plasma protein binding and competition between enantiomers for binding sites could be accommodated. There were substantial differences in the affinity of ibuprofen enantiomers for protein binding sites (RP2=0.358±0.185 vs. SP2=0.979 ±0.501 μg/ml; X±SD) but no differences in their binding capacity (RP1=160±86 vs. SP1=161 ±63 μg/ml). Although statistically significant, the differences in competitive inhibition parameters were more modest (SKI=0.661 ±0.363 vs. RKI=0.436 ±0.210 μg/ml). As a result, the intrinsic binding (i.e.), P1/P2J of R(−)-ibuprofen was greater than S(±)-ibuprofen, and the unbound fraction was significantly greater for S-enantiomer vs. R-enantiomer after a given dose of R-ibuprofen or racemate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45048/1/10928_2005_Article_BF01059767.pd

Comparison of gastrointestinal pH in cystic fibrosis and healthy subjects

The primary objective of this study was to define the pH conditions under which supplemental pancreatic enzyme preparations must function in the upper gastrointestinal tract. The hypothesis was that normal or greater gastric acid output in patients with cystic fibrosis (CF), combined with low pancreatic bicarbonate output, results in an acidic duodenal pH, compromising both dosage-form performance and enzyme activity. Gastrointestinal pH profiles were obtained in 10 CF and 10 healthy volunteers under fasting and postprandial conditions. A radiotelemetric monitoring method, the Heidelberg capsule, was used to continuously monitor pH. Postprandial duodenal pH was lower in CF than in healthy subjects, especially in the first postprandial hour (mean time greater than pH 6 was 5 min in CF, 11 min in healthy subjects, P <0.05). Based on the dissolution pH profiles of current enteric-coated pancreatic enzyme products, the duodenal postprandial pH in CF subjects may be too acidic to permit rapid dissolution of current enteric-coated dosage forms. However, the pH was above 4 more than 90% of the time on the average, suggesting that irreversible lipase inactivation in the duodenum is not likely to be a significant limitation to enzyme efficacy. Overall results suggest that slow dissolution of pH-sensitive coatings, rather than enzyme inactivation, may contribute to the failure of enteric-coated enzyme supplements to normalize fat absorption.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44403/1/10620_2005_Article_BF01296029.pd