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Front cover -- IFC -- Textbook of Critical Care -- Copyright page -- Dedication -- Contributors -- contributors, online chapters -- Preface -- Instructions for online access -- Table of contents -- Online contents -- Part 1: Common Problems in the ICU -- Chapter 1: Sudden Deterioration in Neurologic Status -- ? Impairment in Consciousness -- ? Stroke and Other Focal Neurologic Deficits -- ? Seizures -- ? Generalized Weakness and Neuromuscular Disorders -- ? Neurologic Complications of Procedures and Treatments -- ? Evaluation of Sudden Neurologic Change -- ? Monitoring for Neurologic Changes -- Annotated References -- References -- Chapter 2: Agitation and Delirium -- ? Agitation -- ? Delirium -- ? Pathophysiology -- ? Assessment -- ? Management -- ? Summary -- Annotated References -- References -- Chapter 3: Management of Acute Pain in the Intensive Care Unit -- ? Acute Pain Assessment -- ? Options for Acute Pain Therapy -- Annotated References -- References -- Chapter 4: Fever and Hypothermia -- References -- Chapter 5: Very High Systemic Arterial Blood Pressure -- ? Pathophysiology -- ? Cerebrovascular Disease -- ? Cardiovascular Disease -- ? Renovascular Disease -- ? Excess Catecholamine States -- ? Miscellaneous Conditions -- ? Antihypertensive Medications -- ? Miscellaneous Medications -- ? Summary -- Annotated References -- References -- Chapter 6: Low Systemic Arterial Blood Pressure -- ? Initial Evaluation -- ? What Is the Cause? -- ? Treatment -- Annotated References -- References -- Chapter 7: Tachycardia and Bradycardia -- Annotated References -- References -- Chapter 8: Arterial Hypoxemia -- ? Reduced Alveolar Oxygenation -- ? Diffusion Abnormalities -- ? Ventilation/Perfusion Mismatch -- ? Alveolar-Arterial Partial Pressure of Oxygen Gradient -- ? Reduced Mixed Venous Oxygen -- References -- Chapter 9: Acute Respiratory Failure.
Background Stiripentol (STP) is an antiepileptic drug which efficacy has been demonstrated in severe myoclonic epilepsy and strongly suggested in partial epilepsy as an add-on therapy. A pharmacokinetic (PK) study was performed in healthy volunteers as the linearity of STP PK remains controversial. Methods A randomised double blind cross-over study at 3 different single oral doses (500, 1000, 2000 mg as tablets) was performed in 12 subjects. Sixteen blood samples were collected in each subject. STP plasma concentrations were determined by HPLC. Data were analysed using a compartmental analysis. Results A two-compartment model with a zero order absorption (R0) and a significant lag-time fitted the data. The following parameters were calculated: Cmax (3.1±0.9, 7.1±1.9,13.2±3.6 mg/l), R0 (356±194,742±634, 871±362 mg/h), Cl/F (58±28, 33±10, 25±8 l/h), AUC 0-inf (9.3±3.4, 33.1±10.9, 87.6±27.7 mg.h/l) and T1/2β (4.4±2.1, 10.1±3.3, 13.7±6.2 h) after the 500, 1000 and 2000 mg dosages respectively. Dose-normalized Log10 (AUC) were found significantly different (p< 10−10, ANOVA) between groups. However the half-life was not significantly different between the 1000 and the 2000 mg dosage. Conclusion A dose-dependent non-linear STP PK can be concluded, probably due to an increase in bioavailability, possibly a saturable first-pass effect. However stable concentrations are expected at steady-state as the elimination phase is linear (first order). Clinical Pharmacology & Therapeutics (2005) 77, P64–P64; doi: 10.1016/j.clpt.2004.12.134
info:eu-repo/semantics/published
