The pharmacokinetic parameters of gentamicin and tobramycin were evaluated and compared for 260 patients with pleural effusions and 1,049 patients without pleural effusions by chest radiograph. Pharmacokinetic data were collected prospectively and analyzed by using our aminoglycoside data base. Univariate analysis revealed that the patients with pleural effusions demonstrated significantly lower serum albumin concentrations, greater aminoglycoside volumes of distribution, longer elimination half-lives, and lower peak and higher trough concentrations in serum than the patients without pleural effusions. Patients with pleural effusions were significantly older and had lower total body weight. Stepwise multiple linear regression analysis revealed that lower total body weight and serum albumin concentration, presence of pleural effusion, and greater age were associated with significantly greater volumes of distribution. Calculated creatinine clearance, age, total body weight, and shock were associated with reduced aminoglycoside clearance in these patients.Despite the increased availability of extended-spectrum beta-lactam and fluorinated quinolone antimicrobial agents, the aminoglycosides remain an important group of antibiotics in the treatment of severe gram-negative infections (6). Individualization of aminoglycoside dosing by determining serum drug concentrations has been employed as a means of maximizing efficacy while minimizing drug toxicity (2, 13, 15). Over the past few years, however, several disease states and clinical conditions have been demonstrated to alter aminoglycoside pharmacokinetics from normally accepted parameters (4,7,14,(19)(20)(21)(22). Several authors have demonstrated that these highly polar compounds are capable of penetrating the pleural cavity and can be detected in pleural fluid (8, 9). It is possible that patients with pleural effusions possess altered pharmacokinetic parameters for aminoglycosides. The purpose of our investigation was to assess and describe the pharmacokinetics of these agents for two discrete adult populations: patients with pleural effusions demonstrable by chest radiograph and patients without pleural effusions by chest radiograph. In addition, since hypoalbuminemia has been shown to affect aminoglycoside pharmacokinetics (20), the serum albumin concentrations for these patients were examined to determine whether this nutritional deficiency was an important cofactor or whether pharmacokinetic alterations exist for patients with hypoalbuminemia.This investigation utilized data which were collected prospectively by the Clinical Pharmacy Service of The Mary Imogene Bassett Hospital from January 1983 through August 1991. Patients eligible for the study included all adult patients (ages 18 years or older) who received either gentamicin or tobramycin and who had no pathophysiology (aside from impaired renal function) known to alter aminoglycoside pharmacokinetics (4,11,19,21,22 Within 72 h of the initiation of treatment with the antibiotic, aminoglycoside pharmacokine...
A prospective, randomized, crossover study was performed with seven healthy volunteers to address the effect of increased gastric pH on dapsone absorption. Subjects were randomized to receive a single 100-mg dose of dapsone or a single 100-mg dose of dapsone in addition to 30 ml of a high potency antacid 1 h before dapsone administration and hourly thereafter for a total of 10 doses. Dapsone concentrations in serum were measured periodically for 48 h. No statistical differences between the two regimens were noted when mean dapsone maximal initial concentrations, times to peak, and areas under the curve were compared. These data suggest that an increase in gastric pH has little or no effect on the absorption of dapsone in healthy subjects.Dapsone is frequently employed in the prophylaxis and treatment of Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus (4, 13). Metroka et al. reported that dapsone's efficacy was significantly reduced in patients who received concomitant didanosine therapy. The mechanism postulated for this interaction was that the buffering agents in didanosine elevated gastric pH, resulting in decreased dapsone absorption (12). This hypothesis was based on in vitro findings that have shown dapsone to be insoluble in a neutral pH environment and completely soluble in an acidic environment (17). Since this report, the effect of increased gastric pH on dapsone absorption has been debated (7,8).The speculation that dapsone may require an acidic environment for absorption is potentially significant, especially in AIDS patients, since achlorhydria has been described in this population (9-11). However, clinical studies to evaluate the absorption characteristics of dapsone in the presence of elevated gastric pH have not yet been performed. As such, this prospective, crossover study was performed with healthy volunteers to evaluate the effect of increased gastric pH via concomitant antacid administration on dapsone absorption.The study protocol was approved by the Institutional Review Boards at Nassau County Medical Center and St. John's University. Healthy volunteers over 18 years old were enrolled after giving informed written consent. The study subjects underwent an initial physical exam as well as a routine serum chemistry work-up which included routine laboratory monitoring. Additionally, their glucose-6-phosphate dehydrogenase level was evaluated. Human chorionic gonadotropin levels in blood and urine were evaluated prior to the first and second stages of study for all female subjects. Subjects were excluded from the study if they (i) were taking any scheduled medications; (ii) had an estimated creatinine clearance of less than 30 ml/min as determined by the equation of Cockcroft and Gault (5); (iii) had liver impairment, which was defined biochemically by liver function test results reported to be greater than two times higher than laboratory normal values or by a history of end-stage liver disease and/or cirrhosis; (iv) had a known
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