Population pharmacokinetics of methylprednisolone in accident victims with spinal cord injury
| Autor: | Jürgen Barth, Möllenhoff G, Balbach S, Winkler J, Madabushi R, Hartmut Derendorf, Schumann R, Helmut Möllmann, Nagaraja Nv |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Saliva Adolescent Population Anti-Inflammatory Agents Loading dose Methylprednisolone Bolus (medicine) Pharmacokinetics Medicine Humans Pharmacology (medical) Methylprednisolone Hemisuccinate education Infusions Intravenous Chromatography High Pressure Liquid Spinal Cord Injuries Aged Pharmacology Body fluid Aged 80 and over education.field_of_study business.industry Middle Aged NONMEM Anesthesia Accidents Area Under Curve Female business medicine.drug |
| Zdroj: | International journal of clinical pharmacology and therapeutics. 42(9) |
| ISSN: | 0946-1965 |
| Popis: | OBJECTIVE High-dose methylprednisolone (MP) is used to treat acute spinal cord injury (ASCI). The objective of the present study was to determine the pharmacokinetics of the pro-drug methylprednisolone hemisuccinate (MPHS) and MP in accident victims with ASCI. METHODS The patients (n = 26) were treated with a bolus intravenous loading dose of 30 mg/kg MPHS within 2 h after injury and this was followed by a maintenance infusion of 5.4 mg/kg/h up to 24 h. Blood, CSF and saliva samples were collected up to 48 h after the initial dose and the samples were analyzed by HPLC. Concentration-time data of MPHS and MP were analyzed using population pharmacokinetic analysis with NONMEM software. RESULTS MPHS and MP could be monitored in plasma and CSF. MP but not MPHS was present in saliva. High variability was seen in the MPHS levels in CSF. The pharmacokinetics of the pro-drug and the metabolite were adequately described by a 2-compartment model with exponential distribution models assigned to the interindividual and the residual variability. At steady state, the average measured MP concentration in plasma was 12.3+/-7.0 microg/ml and 1.74+/-0.85 microg/ml in CSF. The CSF levels of MP could be modeled as a part of the peripheral compartment. CONCLUSION This study demonstrated that CSF concentrations of MP were sufficiently high after i.v. administration and reflected the concentrations of unbound drug in plasma. Salivary levels of MP were about 32% of the plasma level and may serve as an easily accessible body fluid for drug level monitoring. |
| Databáze: | OpenAIRE |
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