Nadia Jebabli

Methotrexate Side Effects: Review Article

Methotrextae (MTX) is an antifolate first developed to treat certain types of cancer. It was used at higher doses as a cancer therapy and since 1990 it is used at much lower doses to treat rheumatic diseases [1]. Side effects of MTX high dose (MTX-HD) may be life threatening, however those of various doses of oral MTX are variable because of the interindividual variability of gastrointestinal absorption of this drug. Bone marrow, gastrointestinal mucosa and hair are particularly vulnerable to the effects of MTX, secondary to their high rate of cellular turnover [2] and because MTX concentration is inversly proportianal to renal clearance [2], renal toxicity is frequent with MTX-HD.

Estimation of Abbreviated Cyclosporine A Area under the Concentration-Time Curve in Allogenic Stem Cell Transplantation after Oral Administration.

Measurements of Cyclosporine (CsA) systemic exposure permit its dose adjustment in allogenic stem cell transplantation recipients to prevent graft-versus-host disease. CsA LSSs were developed and validated from 60 ASCT patients via multiple linear regressions. All whole-blood samples were analyzed by fluorescence polarization immunoassay (FPIA-Axym). The 10 models that have used CsA concentrations at a single time point did not have a good fit with AUC0–12 (R2 < 0.90). C 2 and C 4 were the time points that correlated best with AUC0–12 h, R2 were respectively 0.848, and 0.897. The LSS equation with the best predictive performance (bias, precision and number of samples) utilized three sampling concentrations was AUC0–12 h = 0.607 + 1.569 × C 0.5 + 2.098 × C 2 + 3.603 × C 4 (R2 = 0.943). Optimal LSSs equations which limited to those utilizing three timed concentrations taken within 4 hours post-dose developed from ASCT recipients patients yielded a low bias <5% ranged from 1.27% to 2.68% and good precision <15% ranged from 9.60% and 11.02%. We propose an LSS model with equation AUC0–12 h = 0.82 + 2.766 × C 2 + 3.409 × C 4 for a practical reason. Bias and precision for this model are respectively 2.68% and 11.02%.

Delayed Elimination of Methotrexate in a Patient Receiving Ciprofloxacin

High-dose methotrexate (HD-MTX) is indicated in neoplasic diseases. It is administrated at doses above 500 mg/m2 in association with alkaline hyperhydratation and folinic acid in order to interrupt the antifolinic activity of this chemotherapy.[1,2] It has several toxic side effects as mucosal ulcer, hepatitis and renal impairment.[2] This toxicity may be exacerbated by a delayed elimination of HD-MTX. Many factors may lead to the delayed elimination of HD-MTX such as renal impairment, third space fluid collections and drug-drug interactions. Non steroidal anti-inflammatory drugs (NSAIDs), probenicid, penicillin and sulfamethoxazole-trimethoprim are the most responsible of drug interactions with MTX.[3] We report herein a rare case of delayed elimination of HD-MTX associated with administration of ciprofloxacin.

Interaction médicamenteuse entre le tacrolimus et la théophylline chez un greffé rénal : à propos d’un cas

Le tacrolimus est un immunosuppresseur largement indiqué dans la greffe d’organes solides. [1] C’est un médicament métabolisé au niveau du foie par le CYP 450 3A4. De nombreuses interactions médicamenteuses sont observées avec les inducteurs et les inhibiteurs enzymatiques du système cytochrome P450, [2] entraînant dans le premier cas un risque de rejet de greffe par diminution des concentrations sanguines du tacrolimus et dans le second un risque de toxicité par augmentation de ses concentrations sanguines. Les principaux inducteurs enzymatiques interagissant avec le tacrolimus sont les anticonvulsivants, la rifampicine et les extraits de millepertuis. [2,3] Concernant les inhibiteurs enzymatiques, il s’agit essentiellement de macrolides, antiprotéases, antifongiques azolés, antagonistes calciques, amiodarone et inhibiteurs de la pompe à protons. [2,3] Nous rapportons dans ce travail un cas d’interaction médicamenteuse très rarement observé, entre le tacrolimus et la théophylline.

Vancomycin Therapeutic Drug Monitoring in Cerebrospinal Fluid

Vancomycin penetrates poorly through the blood-brain barrier. Determination of vancomycin concentration in plasma is recommended. In contrast, its determination in cerebrospinal fluid (CSF) is rarely performed. We report the case of a 74-year-old man with post traumatic meningitis with vancomycin concentration measured in CSF.

Population pharmacokinetics of bupivacaine in combined lumbar and sciatic nerve block

Objectives: The primary aim of this study was to establish the population pharmacokinetic (PPK) model of bupivacaine after combined lumbar plexus and sciatic nerve blocks and secondary aim is to assess the effect of patients characteristics including age, body weight and sex on pharmacokinetic parameters. Materials and Methods: A total of 31 patients scheduled for elective lower extremity surgery with combined lumbar and sciatic nerve block using plain bupivacaine 0.5% were included. The total bupivacaine plasma concentrations were measured before injection and after two blocks placement and at selected time points. Monitoring of bupivacaine was made by high performance liquid chromatography (HPLC) with ultraviolet detection. Non-linear mixed effects modeling was used to analyze the PPK of bupivacaine. Results: One compartment model with first order absorption, two input compartments and a central elimination was selected. The Shapiro-Wilks test of normality for normalized prediction distribution errors for this model (P = 0.156) showed this as a valid model. The selected model predicts a population clearance of 930 ml/min (residual standard error [RSE] = 15.48%, IC 95% = 930 ± 282.24) with inter individual variability of 75.29%. The central volume of distribution was 134 l (RSE = 12.76%, IC = 134 ± 33.51 L) with inter individual variability of 63.40%. The absorption of bupivacaine in two sites Ka1 and Ka2 were 0.00462/min for the lumbar site and 0.292/min for the sciatic site. Age, body weight and sex have no effect on the bupivacaine pharmacokinetics in this studied population. Conclusion: The developed model helps us to assess the systemic absorption of bupivacaine at two injections sites.

Hypericum Humifusum Leaves Attenuates Hepatic Ischemia-Reperfusion Injury in a Rat Model

INTRODUCTION Effective prevention strategies require specific actions during the different phases of ischemia-reperfusion (I-R) injury. The objective of our study is to evaluate the effect of aqueous extract of Hypericum humifusum leaves (HHL) on liver I-R model in Rat. MATERIAL AND METHODS Animals were subjected to 90 min of hepatic ischemia followed by reperfusion (120 min). HHL extract (25 mg/mL/kg) was injected 15 min before reperfusion. To evaluate the effect of HHL extract on I-R, we have monitored transaminases levels, Malondialdehyde (MDA) concentration, histological lesions (apoptosis and necrosis) and compared the results to a reference oxidant vitamin E. RESULTS The determination of total phenol extracts of HHL was 59.91 ± 0.35 mg of Gallic Acid/g dry plant material with higher antioxidant activity (91.73% ± 1.67) compared to vitamin E (87.42%). Using aqueous extract of HHL, we noted a significant decrease of AST and ALT [1129 UI (585/1995) and 768 UI (335/1375)] compared to no-treated group [5,585.5 UI (5,035/12,070) and 8,099.5 UI (5,040/12,326)] as a decrease in MDA content [85.7% protection (50.9/91.5)]. HHL extract reduce the damage induced by I-R of 48.7% (27/48.7) and 96.1% (95.7/96.5) for necrosis and apoptosis lesions respectively. CONCLUSION HHL aqueous extract have potential to protect liver from the damage effect induced by I-R better than vitamin E solution.INTRODUCTION Effective prevention strategies require specific actions during the different phases of ischemia-reperfusion (I-R) injury. The objective of our study is to evaluate the effect of aqueous extract of Hypericum humifusum leaves (HHL) on liver I-R model in Rat. MATERIAL AND METHODS Animals were subjected to 90 min of hepatic ischemia followed by reperfusion (120 min). HHL extract (25 mg/mL/kg) was injected 15 min before reperfusion. To evaluate the effect of HHL extract on I-R, we have monitored transaminases levels, Malondialdehyde (MDA) concentration, histological lesions (apoptosis and necrosis) and compared the results to a reference oxidant vitamin E. RESULTS The determination of total phenol extracts of HHL was 59.91 ± 0.35 mg of Gallic Acid/g dry plant material with higher antioxidant activity (91.73% ± 1.67) compared to vitamin E (87.42%). Using aqueous extract of HHL, we noted a significant decrease of AST and ALT [1129 UI (585/1995) and 768 UI (335/1375)] compared to no-treated group [5,585.5 UI (5,035/12,070) and 8,099.5 UI (5,040/12,326)] as a decrease in MDA content [85.7% protection (50.9/91.5)]. HHL extract reduce the damage induced by I-R of 48.7% (27/48.7) and 96.1% (95.7/96.5) for necrosis and apoptosis lesions respectively. CONCLUSION HHL aqueous extract have potential to protect liver from the damage effect induced by I-R better than vitamin E solution.

Contribution of Therapeutic Monitoring in the Assessment of Toxic Adverse Effects of Mitotane: a Case Report

Mitotane provided serious side effects and low doses seemed to be tolerated. Determination of mitotane concentration in plasma is recommended. We report the case of toxic plasma levels with low doses of mitotane in a 47-year-old man with adrenocortical cancer.

Raccourcissement accidentel du temps de perfusion de méthotrexate à haute dose : cas clinique et revue de la littérature

Methotrexate (MTX) is a folic acid antagonist used at high-dose intravenously on 24 hours (24h) in the treatment of the acute lymphoblastic leukemia (ALL). To prevent potential toxicity, MTX is usually administered following the application of preventive measures. We report a case of an accidental shortening time for high dose MTX infusion and a literature review of accidental intoxications by the MTX. This case illustrates the importance of the respect of MTX high dose infusion time and the major role played by the therapeutic drug monitoring.