Int J Clin Pharm Th
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Int J Clin Pharm Th · Oct 2002
Clinical TrialPharmacokinetics of levosimendan and its metabolites during and after a 24-hour continuous infusion in patients with severe heart failure.
Levosimendan is a new calcium sensitizer with additional vasodilatory properties developed for the short-term intravenous treatment of congestive heart failure. The aims of the present study were to determine the pharmacokinetics and hemodynamic effects of levosimendan and its metabolites during and after a 24-hour levosimendan infusion. ⋯ A 24-hour infusion of levosimendan induces hemodynamic effects lasting several days after stopping the infusion. The prolongation of the effects beyond the infusion period is most likely due to an active metabolite with a long half-life.
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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 · Dec 2009
Clinical TrialPharmacokinetics and clinical toxicity of prilocaine and ropivacaine following combined drug administration in brachial plexus anesthesia.
Local anesthetics (LA) are often administered in combination for regional anesthesia in order to obtain the specific advantages (onset and duration of effect) of each drug. However, few data on the safety of such combinations are available and consequently plasma concentrations possibly associated with toxicity and interactions between the specific anesthetics are not sufficiently established. We measured pharmacokinetics and toxicity parameters of prilocaine and ropivacaine after combined use as single doses in brachial plexus blockade. ⋯ The use of a combined prilocaine/ ropivacaine (300 mg/75 mg) dose regimen in patients given single dose for brachial plexus blockade can generally be regarded as safe with regard to peak plasma concentrations and cardiovascular toxicity and this holds true for patients with a higher perioperative risk profile (ASA III grading, American Society of Anesthesiologists). The considerable inter-individual variation in LA peak plasma concentrations observed in our patients and the one case of suspected accidental intravascular injection, highlight the necessity of adequate monitoring of the patients undergoing LA injections.
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Int J Clin Pharm Th · Nov 2012
Prediction of distribution volume of vancomycin in critically ill patients using extravascular lung water and pulmonary vascular permeability indices.
Alterations in distribution volume affect the concentrations of hydrophilic drugs in plasma and tissues at the time of initial therapy. When the distribution volume of hydrophilic antimicrobials is increased in critically ill patients with a serious infection, antimicrobial concentrations are reduced, which may adversely affect the efficacy of antimicrobial therapy. A transpulmonary thermodilution technique system (PiCCO) enables measurements of pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI), which are related to pulmonary edema and pulmonary vascular permeability, respectively. In addition, those indices may also be related to the distribution volume of hydrophilic antimicrobials. The aim of this study was to investigate the relationships of PVPI and EVLWI with the distribution volume of vancomycin (Vss), as well as to establish a method for estimating Vss for planning an appropriate initial dose for individual patients. ⋯ EVLWI determined by the PiCCO system is useful to predict Vss and should lead to more effective vancomycin therapy for critically ill patients at the initial stage.
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Int J Clin Pharm Th · Jan 2007
Comparative StudyComparison of plasma and saliva concentrations of levetiracetam following administration orally as a tablet and as a solution in healthy adult volunteers.
Concentrations in saliva, as an alternative to concentrations in blood, can be advantageous for the monitoring of antiepileptic agents. This study assesses the relationship between saliva and plasma concentrations of levetiracetam after administration orally as a solution and as a tablet. The possibility that saliva concentrations of the drug are altered by contamination in the buccal cavity was also examined. ⋯ Using saliva to monitor therapeutic exposure to levetiracetam is feasible beginning 15 minutes after tablet intake but beginning 4 hours after intake of an oral solution.