Issam Salouage

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.

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.

Limited sampling strategy for the estimation of mycophenolic acid area under the curve in Tunisian renal transplant patients

Mycophenolate mofetil is a prodrug widely used in renal transplantation to prevent organ rejection. It is hydrolyzed to its active compound mycophenolic acid (MPA). MPA area under the curve (AUC0-12h) is considered the best pharmacokinetic parameter for the estimation of MPA exposition and for prediction of rejection. MPA-AUC requires several blood samples, making it impractical for clinical practice. Therefore, development of a limited sampling strategy (LSS) to estimate MPA AUC0-12h using three blood samples is very helpful for MPA individual dose adjustment. Results of LSS differ according to the patient background and to the drug formulation. Therefore, the purpose of this study was to develop a LSS for the estimation of MPA AUC0-12h in Tunisian renal transplant patients treated with the generic formulation of mycophenolate mofetil (MMF®, MEDIS). The best correlation was achieved by a profile based on three time points C0.5h, C1.5h, and C4h after drug intake: AUC0-12hxa0=xa00.414xa0+xa01.210xa0×xa0C0.5xa0+xa02.256xa0×xa0C1.5xa0+xa04.134xa0×xa0C4 (meixa0=xa01.65% and rmsexa0=xa05.81%). The correlation between full AUC0-12h and abbreviated AUC0-12h was 0.917. In conclusion, this model provides a reliable and simple equation to estimate MPA AUC0-12h for the generic formulation of mycophenolate mofetil (MMF®).

Convulsion tardive après instillation de lidocaïne pour bronchoscopie

INTRODUCTIONnLidocaine toxicity usually appears rapidly and is directly correlated with plasma concentrations of the drug.nnnCASE REPORTnWe report a case of a late neurologic toxicity occurring after instillation of lidocaine during fibre-optic bronchoscopy. A patient with bronchiolitis obliterans underwent a diagnostic bronchoscopy. She received multiples instillations of Xylocaine(®) 2% (lidocaine). Three and a half hours later, she had a tonic-clonic seizure. Seven hours later, this recurred. Lidocaine plasma levels were in the toxic range at the time of the first seizure (18.32μg/mL) with a significant decrease in the concentration noted 24hours later.nnnCONCLUSIONnThe slow absorption of lidocaine into the blood from the bronchial tree explains the delayed neurologic toxicity. Our observation is a reminder that complications can occur due to high doses of lidocaïne administrated by instillation. Thus, if the recommended dose of lidocaine is exceeded, it is essential to monitor patients closely for a prolonged period, especially those with fibrosing lung disease in order to avoid possible late toxicity.

Suivi thérapeutique de l’acide valproïque chez l’enfant : étude prospective de l’effet de l’observance et du niveau économique sur les concentrations plasmatiques résiduelles et les crises épileptiques

INTRODUCTIONnValproic acid (VA) is a widely used antiepileptic drug. Because of its pharmacokinetic variability and the influence of intrinsic and extrinsic factors such as the treatment compliance, VA therapeutic drug monitoring (TDM) is recommended in children. The aim of this study is to evaluate the effect of treatment compliance and the economic level on VA tough plasmatic concentration (TPC) and epileptic rhythm in children.nnnMATERIAL AND METHODSnA one-year prospective study (August 2008-August 2009) concerning children (age≤5 years) regularly treated by VA who had a VA TDM. So, 276 plasmatic samples from 238 children were collected. The children were divided in two groups as following: the group 1 (G1) presenting a good compliance and a reliable questioning and the group 2 (G2) presenting a bad compliance and a non reliable questioning. We evaluated the interindividual variability by correlating the TPC to the dose. Then, we divided the hole group in function of their economic levels (low-medium-high).nnnRESULTSnSex ratio male/female was 1.3. Median age was 5 years+/-3,9. The mean TPC was 62 µg/mL [0.12-131 µg/mL]. VA TPC were in the therapeutic range (TR) in 62%. Adverse drug reactions were noted in 4.2% of the children. G1 represented 70% of the children and G2, 30%. The TPC were in the TR in 67% of G1 and 51% of G2 (p=0.02). There was a significant difference between the TPC in G1 and G2 (p=0.02).There was no significative difference in the TPC in function of the economic levels. There was no correlation between TPC and the administered doses. The epileptic seizures were more spaced in children with therapeutic TPC than those with TPC in the TR (p=0.002) and in G1 than in G2 (p=0.03).nnnCONCLUSIONSnCompliance should be appropriate in order to optimize the TDM rule. A good compliance and a therapeutic TPC allow a better control of epileptic seizures.