DRUG MILK TO SERUM RATIO PREDICTION AND ONTOGENY OF CYP3A CLEARANCE PATHWAY AS A MODEL OF DRUG EXPOSURE IN THE DEVELOPING RAT

Transfer of drugs into milk and the clearance of drugs in neonates are critical determinants of the exposure of infants to drugs in breast milk. Models predicting both parameters have been proposed. The objective of this dissertation is to test two models predicting milk to serum ratio and an ontogeny clearance model predicting clearance in the neonate. Predicted milk to serum ratio (M/S) values were generated according to the Atkinson and Begg model. The model did not adequately predict M/S when comparing the predicted values to observed values in the literature. The Fleishaker model was also tested. The model was able to predict whether the drugs appeared in milk by passive diffusion only or whether active transport processes were involved. This model, together with appropriate animal models, is useful in understanding the mechanism of drug transfer into milk. An ontogeny model that predicts clearance was proposed earlier by our laboratory. In order to test the model prediction and assumptions of constant microsomal protein and constant Km for an enzyme-substrate system with age, the male rat was used as an animal model. The ontogeny of Cyp3a1, Cyp3a2, Mdr1a and Mdr1b mRNA was examined in the male rat liver and intestine. The ontogeny pattern of Cyp3a2 mRNA, protein and in vitro Cyp3a activity were found to be similar in male rat liver. The microsomal protein content was found to vary with age in the liver. Km was found to be constant with age for the midazolam 4-hydroxylation by male rat liver microsomes. Scaling factors that extrapolate adult clearance to infant clearance were calculated from in vitro data. The model did not predict the in vivo oral clearance of midazolam for day 7 and 21 age groups from the 112 day age group (adult). The assumption that intestinal availability in the rat pups and adults was equal to unity might not be true resulting in overprediction of rat pup clearance when compared to the adult. Intestinal first pass effect for midazolam in adult rats might be significant. More experiments are needed to further test the model adequacy in clearance prediction

DRUG MILK TO SERUM RATIO PREDICTION AND ONTOGENY OF CYP3A CLEARANCE PATHWAY AS A MODEL OF DRUG EXPOSURE IN THE DEVELOPING RAT

Transfer of drugs into milk and the clearance of drugs in neonates are critical determinants of the exposure of infants to drugs in breast milk. Models predicting both parameters have been proposed. The objective of this dissertation is to test two models predicting milk to serum ratio and an ontogeny clearance model predicting clearance in the neonate. Predicted milk to serum ratio (M/S) values were generated according to the Atkinson and Begg model. The model did not adequately predict M/S when comparing the predicted values to observed values in the literature. The Fleishaker model was also tested. The model was able to predict whether the drugs appeared in milk by passive diffusion only or whether active transport processes were involved. This model, together with appropriate animal models, is useful in understanding the mechanism of drug transfer into milk. An ontogeny model that predicts clearance was proposed earlier by our laboratory. In order to test the model prediction and assumptions of constant microsomal protein and constant Km for an enzyme-substrate system with age, the male rat was use

Evaluation of the physician’s acceptance to clinical pharmacy interventions after antibiotic stewardship implementation in the ICU in a general hospital in Egypt

Background: Physicians’ perception of the role of the clinical pharmacist role plays a cornerstone in accepting interventions suggested by pharmacists to correct DRPs and in complying with guidelines of a pharmacist-led Antibiotic stewardship program (ASP). This study aimed at evaluating the acceptance of physicians’ to pharmacists interventions to antibiotic prescribing and the change in antibiotic consumption in Al-Haram general hospital Intensive care unit (ICU). Methods: This study was performed in Al-Haram general hospital ICU from July 2014 till December 2015. Medication review of antibiotics started in Al-Haram hospital ICU in July 2014 by responsible clinical pharmacists. An on-job physician education program about antibiotics started in June 2015. Implementation of ASP started in July 2015. The antibiotic related interventions and response of physicians to interventions were recorded all along the study period. The pattern of physicians’ acceptance along with antibiotic consumption (in Daily define dose per 1000 patient-days) were reported. Results: The number of accepted interventions had increased along the study. The overall antibiotic consumption increased after implementation of ASP, however the individual pattern of antibiotic prescribing changed. Conclusion: The physicians in Al-Haram hospital appeared to accept the role of clinical pharmacist in correcting antibiotic-related DRPs as well as in implementing ASP. Keywords: Antibiotic stewardship, Antimicrobial prescribing, Clinical pharmacy, Antibiotic consumption, Physician’s perceptio

Pharmacoeconomic

Community-acquired pneumonia (CAP) is a serious and widespread infection due to its high incidence, morbidity, mortality and increased healthcare costs. This study aimed at investigating antibiotic combination regimen containing fluoroquinolone (Group A) and antibiotic combination regimen not containing fluoroquinolone (Group B) in terms of effectiveness parameters and direct medical costs associated with treatment of CAP patients admitted to Intensive Care Unit (ICU). This study was designed as retrospective and prospective observational studies including CAP patients admitted to the Respiratory ICU. The patients’ files were collected and the effectiveness parameters of outcomes were compared on admission and on discharge. Effectiveness and costs analyses between antibiotic regimens either containing or not containing fluoroquinolone were performed. A total of 16 patients were enrolled in our retrospective study; (Group A) included 7 patients, while (Group B) included 9 patients. The prospective study included 30 patients; (Group A) included 13 patients and (Group B) included 17 patients. There was non-significant difference in the number of days in ICU between the two groups with a trend to shorter length of stay in ICU in (Group B) compared to (Group A) in both retrospective and prospective studies. Cost analysis showed that there was non-significant difference with a trend to lower direct medical costs in (Group B) which resulted in cost savings of (L.E) 1277 and (L.E) 816 for retrospective study and prospective study respectively. In conclusion, regimens containing or not containing fluoroquinolone did not show a significant increase in either effectiveness or costs of CAP treatment in the ICU

Additional file 1 of The effectiveness and pharmacoeconomic study of using different corticosteroids in the treatment of hypersensitivity pneumonitis

Supplementary Material

A specially tailored vancomycin continuous infusion regimen for renally impaired critically ill patients

Background: Vancomycin remains the gold standard for treatment of methicillin-resistant Staphylococcus aureus . Specially designed continuous infusion of vancomycin leads to better therapy. Methodology: A total of 40 critically ill patients who suffered from pneumonia susceptible to vancomycin, had serum creatinine >1.4 mg%, and oliguria <0.5 mL/kg/h for 6 h were included in the study with respiratory culture sensitivity to vancomycin ≤2 mg/L. Patients’ clinical, microbiological, and biological data were obtained by retrospective analysis of the corresponding medical files before and after vancomycin treatment. Patients with serum creatinine level ≥4 mg% and patients who received renal replacement therapy during the treatment period were excluded. The patients were divided into two groups—group 1 (intermittent dosing) and group 2 (continuous infusion) based on the following formula: rate of vancomycin continuous infusion (g/day) = [0.0205 creatinine clearance (mL/min) + 3.47] × [target vancomycin concentration at steady state (µg/mL)] × (24/1000). Trough vancomycin serum levels were also assessed using high-performance liquid chromatographic technique. Patients’ outcomes such as clinical improvement, adverse events, and 15-day mortality were reported. Results: Group 2 showed significant reduction in blood urea nitrogen, creatinine serum levels, white blood cells, partial carbon dioxide pressure, body temperature, and Sequential Organ Failure Assessment score, while significant increase in partial oxygen pressure and saturated oxygen was also observed. A significantly shorter duration of treatment with a comparable vancomycin serum levels was also reported with group 2. Conclusion: After treatment, comparison in patients’ criteria supports the superiority of using continuous infusion of vancomycin according to this equation in renally impaired patients