Preclinical pharmacokinetics of MK-0974, an orally active calcitonin-gene related peptide (CGRP)-receptor antagonist, mechanism of dose dependency and species differences.

The underlying mechanism for low oral bioavailability of MK-0974, a potent calcitonin-gene related peptide (CGRP)-receptor antagonist, in monkeys and for species-dependent non-linear pharmacokinetics in monkeys and rats were investigated. In monkeys, MK-0974 displayed moderate clearance (14-20 ml min(-1) kg(-1)), while oral bioavailability was 6%. The pharmacokinetics of MK-0974 remained linear across 0.5-10 mg kg(-1) intravenous dose in monkeys, but the oral area under the plasma concentration-time curve (AUC) increase (5-30 mg kg(-1)) was 15-fold over dose-proportional. Based on a comparison of AUC following hepatic portal vein administration and cephalic vein infusion, MK-0974 exhibited a low-to-moderate hepatic extraction ratio (36%) in monkeys. Following oral dose of [14C]MK-0974 to monkeys, the hepatic portal AUC ratio of MK-0974 versus total radioactivity was 0.32, and the total radioactivity recovered in bile and urine was 45-83%. MK-0974 undergoes significant oxidative metabolism (cytochrome P450 (CYP) 3A) in monkey intestinal microsomes. In contrast, oral AUC of MK-0974 in rats was near dose-proportional (15-100 mg kg(-1)). Following oral administration of [14C]MK-0974 to rats, the hepatic portal AUC ratio of MK-0974 to total radioactivity (0.67) was higher than in monkeys. Additionally, the metabolic rate of MK-0974 was slower in rat than in monkey intestinal microsomes. Collectively, intestinal first-pass metabolism played a significant role in the low oral bioavailability in monkeys and contributed to the species-dependent non-linear oral pharmacokinetics in rats and monkeys of MK-0974.

QA methods improve quality of cholera / acute diarrhea care in local health districts in Ecuador.

PIP: The Ministry of Health (MOH) in Ecuador in 1993 received Quality Assurance Program (QAP) technical assistance in initiating a demonstration project aimed at applying quality assurance methods to the case management of cholera and acute diarrhea. The purpose of the project was to demonstrate the feasibility of attaining objective improvements in the quality of care of cholera/acute diarrhea patients at the health district level, to train management teams to use quality assurance (QA) methods and techniques, and to institutionalize QA as part of routine management after the end of the project. The health area of Babahoyo with its 80-bed hospital and eleven health centers, and the health area of La Troncal which includes twelve health centers were selected to participate in the project's activities. Both health areas are located in the coastal region of Ecuador and serve the mostly poor peasant population. This article reports on QA experiences working in nineteen ambulatory health centers of the two health areas. The intervention model provides the health areas with a technical approach and basic tools which will allow health workers and managers to systematically examine the quality and quantity of their work, identifying weaknesses and attaining improvements.^ieng

Reducing patient waiting times through quality assurance methods in La Troncal, Ecuador.

Long patient waiting time is a common problem in hospitals and urban health centers in Ecuador and elsewhere. Besides being a leading cause of patient dissatisfaction with health service quality, it is often related to short doctor-patient contact times that in turn can seriously reduce the technical quality of care. This article describes a quality improvement effort undertaken by the staff of the La Troncal Health Center in Ecuador, with the assistance of a quality assurance project of the University Research Corporation and the Ecuadorian Ministry of Health. Data on patient waiting times was collected and analyzed, and solutions were devised and implemented using quality assurance techniques. As a result, the average patient's total waiting time fell from 116 minutes per visit to 66, and his or her contact time with health center staff members increased from 11 minutes to 16. It appears that the methods and techniques applied have potential for use elsewhere, because they can be applied easily by health personnel, and their cost of implementation is relatively low.