Int J Clin Pharm Th
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A case of rhabdomyolysis, in which the etiology could be associated with phenytoin administration is presented and guidelines are described which may assist the early recognition, treatment and prevention of renal failure when such patients are treated in intensive care units. A 46-year-old white man experienced a generalized tonic-clonic seizure at home lasting approximately two minutes. The patient presented with similar crises when seen by the emergency services and had a neurological status of seven points on the Glasgow scale. He was intubated orotracheally and mechanically ventilated. Administration of a 1,250 mg loading dose of phenytoin in 250 ml 0.9% sodium chloride injection were administered intravenously according to guidelines approved by the hospital. These require administration of the loading dose over 30 - 60 minutes followed by phenytoin 150 mg/8 h i.v. administered as a drip diluted in 0.9% NaCl 50 ml over 30 - 60 minutes. Obtained plasma levels were within the therapeutic range but on Day 3 the level of creatine kinase (CK) increased. We initiated treatment to prevent renal failure but the level doubled daily reaching a peak of 54,000 U/I on the fifth day. It was suspected that the increase in CK was due to the treatment with phenytoin which was stopped and replaced by valproic acid 500 mg/8 h orally. The cumulative total dose of phenytoin was 3,050 mg. The subsequent serial determinations of CK showed a decrease beginning on the day phenytoin was stopped and levels falling to 14,229 U/l on the day the patient left the ICU. The patient had no recurrence of the convulsive episodes after the day of admission. In the neurology ward, the patient recovered satisfactorily and the CK value gradually returned to normal. The patient was asymptomatic when released on the ninth day. ⋯ The most likely cause of the rhabdomyolysis was phenytoin treatment because of the close temporal relationship between exposure to the drug and onset of symptoms and the rapid resolution of the symptoms and signs after phenytoin was discontinued. An objective causality assessment concluded that a possible adverse drug reaction had occurred.
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Int J Clin Pharm Th · Aug 2005
Randomized Controlled Trial Clinical TrialCefepime in critically ill patients: continuous infusion vs. an intermittent dosing regimen.
The aim of this study was to compare the pharmacokinetic and pharmacodynamic parameters of a continuous infusion of cefepime vs. an intermittent regimen in critically ill adult patients with Gram-negative bacilli infection. The prospective randomized parallel study was carried out in 50 patients with severe pneumonia (n = 41) or bacteremia (n = 9). They received cefepime 4 g/d either as a continuous infusion or intermittent administration 2 x 2 g in combination with amikacin. ⋯ The mean time over the French breakpoint (4 mg/l) was 100 +/- 0% and 72 +/- 27% in Group 1 and 2 (p < 0.001), respectively. In contrast to intermittent cefepime administration, continuous infusion of cefepime consistently maintained a serum concentration > 5 x the MIC of typical Gram-negative nosocomial pathogens. This results in greater bactericidal activity against organisms with a higher (2 mg/l) cefepime breakpoint even if the clinical outcome is not significantly modified.
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Int J Clin Pharm Th · Jun 2005
Randomized Controlled Trial Clinical TrialSafety, tolerability and pharmacokinetics of oral S-3304, a novel matrix metalloproteinase inhibitor, in single and multiple dose escalation studies in healthy volunteers.
A novel sulfonamide derivative, S-3304, was discovered as a potent matrix metalloproteinase (MMP) inhibitor. It is a more specific inhibitor to MMP-2 and MMP-9 (in vitro) than to MMP-1, and may therefore lack the musculoskeletal side effects seen with non-specific inhibitors. The aim of the present study was to investigate the safety, tolerability and pharmacokinetics of S-3304 when administered as single and multiple oral doses to healthy male volunteers. ⋯ S-3304 demonstrated a good safety profile and good systemic exposure when administered orally up to 800 mg b.i.d. during 10 - 17 days. At the highest dose level of 800 mg b.i.d., it was free of rheumatoid arthritis-like symptoms.
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Owing to the great progress in clinical chemistry connected with utilization of applied mathematics, pharmacokinetics came into being. The unknown objective methods of research of drugs in human were discovered, among them controlled clinical trials (CCT). These new methodologies generated a new clinical discipline called clinical pharmacology (CPH) which has its roots in basic pharmacology but was applied in clinical specialties. ⋯ There is also an urgent necessity of new legislative acts. These proposals are very general and deficient. They were presented here to conclude this article on the present status of clinical pharmacology with the statement that the real threat for this discipline exists.
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Int J Clin Pharm Th · Oct 2004
Clinical Trial Controlled Clinical TrialTolerability, pharmacokinetics and concentration-dependent hemodynamic effects of oral CF101, an A3 adenosine receptor agonist, in healthy young men.
To assess safety, tolerability, pharmacokinetics and hemodynamic effects of oral CF 101, an A3 adenosine receptor (A3AR) agonist, in healthy men. ⋯ Single oral doses up to 5 mg CF101 and repeated doses up to 4 mg 12-hourly for 7 days were safe and well-tolerated. Multiple-dose CF101 pharmacokinetics were unchanged and predictable from single-dose estimates, and were linearly proportional to dose. Increases in heart rate and neutrophil count were reversible during multiple dosing and were not dose-limiting in the repeat dose study. CF101 warrants further study for its efficacy in treating human disease.