Cefepime in intensive care unit patients: validation of a population pharmacokinetic approach and influence of covariables.

AIM: The purpose of our study was to define and validate a population-pharmacokinetic model including the influence of patients' characteristics on the pharmacokinetics of cefepime. PATIENTS AND METHODS: A total of 55 patients were randomized in Group 1 (34 patients, 320 cefepime concentrations) for the model building and Group 2 (21 patients, 196 cefepime concentrations) for the validation group. They received cefepime as 2 g A 2 or as 4 g continuously. The population pharmacokinetic analysis was carried out using NONMEM and a baseline model was constructed for studying the influence of demographic and biological variables. The model was then validated by a comparison of the predicted and observed concentrations in Group 2. A final model was elaborated from the whole population. RESULTS: Total clearance (CL) was significantly correlated with the serum creatinine (CREA) and the central volume of distribution (V1) was correlated with the body weight (WT). The final model was: CL = 7.14 + (-0.0133 A CREA). V1 = (-16.8) + (0.475 A WT). Q (intercompartmental clearance) = 10.5. V2 = 18.1. The mean pharmacokinetic parameters and their individual variability were: CL (8.24 l/h, 45%), V1 (20.89 l, 60%), V2 (17.95 l, 49%), total volume (38.85 l, 42%) and Q (10.56 l/h, 9%). The bias (1.07 mg/l, IC 95% = -40.46 -+42.60), precision (21.19%) and AFE (1.15) demonstrated the performance of the model. CONCLUSION: We have developed and validated a pharmacokinetic model to estimate cefepime concentrations. We showed that serum creatinine and body weight are factors that may influence the standard dose of cefepime. Our model enabled us to predict cefepime concentrations in other patients.

[Socio-cultural determinants of the lateness of the first prenatal consultation in a health district in Senegal]. / Determinants socioculturels du retard de la 1re consultation prénatale dans un district sanitaire au Sénégal.

OBJECTIVE: to evaluate the socio-cultural determinants of the delay in having the first pre-natal exam (CPN) in order to make recommendations which aim to reduce maternal and fetal morbidity and mortality in the Richard-Toll health district in Senegal. METHOD: the study was cross-sectional, descriptive and analytical, and was conducted on the entire population of pregnant women who came in for a CPN between March 1st and April 30th, 2003. A questionnaire which was developed on the basis of studied variables steered the interview process which was carried out upon completion of each pregnant woman's CPN in 15 different health facilities. Data were recorded and analysed using Epi Info 6.04d software. RESULTS: The sample population studied included 351 pregnant women. The cultural environment over the unexpected nature of the pregnancy, the discretion surrounding the pregnancy, the ignorance of the risks, and the refusal to be examined by male health workers all have a statistically significant influence on the tardiness of the first CPN. Similarly, the late CPN has a statistically strong link with three distinctive elements of the pregnant woman's social profile: namely, illiteracy, at risk age (< 18 or > 34 years old), and total number of deliveries (> 3 births). Illiteracy has a statistically significant link with the refusal to be examined by a male health worker, ignorance of the risks, unexpected pregnancies, and trying to hide one's pregnancy, which has an additional link with the age at risk. DISCUSSION: the social profile of the pregnant women studied is quite similar to that of greater population from which they come. The early CPN allows the care provider to forecast the delivery date with greater presicion and to estimate the delivery conditions more accurately at the time of the fourth CPN at which time the risk for potential complications which may necessitate a Ceasarean section is thoroughly assessed (DRS). Thus, the delay of the first CPN constitutes a limiting factor in the correct monitoring and surveillance of the pregnancy. The various social and cultural factors are intricately intertwined, and this interaction supports the need for multi-sectoral and multi-disciplinary actions which are generally necessary for the resolution of public health problems. Three recommendations are proposed which aim to improve the frequency of the early CPN. CONCLUSION: the influence of socio-cultural factors on the CPN requires that the CPN be fully integrated into a more advanced strategy and that a behaviour change within the community be influenced and take place through health education.