Therapeutic drug monitoring
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Randomized Controlled Trial
A population pharmacokinetic model of epidural lidocaine in geriatric patients: effects of low-dose dopamine.
The purposes of this study were to develop a population pharmacokinetic (PK) model of epidural lidocaine in geriatric patients, to search for any difference in the PK behavior of epidural lidocaine when dopamine is given concurrently, and to develop a descriptive PK model from which to calculate dosage and infusion regimens of epidural lidocaine to define and achieve desired target goals in either the epidural or the serum compartment. Twenty patients over age 65 years, undergoing peripheral vascular surgery using continuous epidural lidocaine anesthesia, were studied. Ten patients also received an intravenous infusion of placebo (normal saline), whereas 10 other patients received an intravenous infusion of dopamine at 2 mug/kg per minute. ⋯ Serum lidocaine concentrations were slightly less in the patients receiving dopamine. Dosage requirements (overall hourly weight-adjusted infusion rates) were slightly less for the patients receiving dopamine, consistent with the slower removal of lidocaine from the epidural compartment. This model should be useful to design more optimal and individualized epidural lidocaine infusion regimens to define and achieve desired target goals in the epidural or the serum compartment.
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Mycophenolate mofetil is an immunosuppressant commonly used in solid organ transplantation. Its active metabolite, mycophenolic acid (MPA), is metabolized to the inactive 7-O-mycophenolic acid glucuronide (MPAG) and the active acyl glucuronide (AcMPAG). Most pharmacokinetic (PK) studies have been focused on MPA, but not its metabolites, in kidney transplant recipients. ⋯ There was wide interpatient variability of MPA, MPAG, and AcMPAG PKs with coefficients of variation exceeding 70% for most PK parameters measured. Other findings (P < 0.05) included: lower MPA area under the curve, maximum concentration, and minimum concentration; higher apparent clearance and MPAG/MPA metabolic ratio in the lung versus heart transplant group; lower MPA area under the curve and minimum concentration, and higher apparent clearance and MPAG/MPA metabolic ratio in lung transplant recipients concurrently taking cyclosporine versus tacrolimus; and lower minimum concentration in heart transplant recipients taking cyclosporine versus tacrolimus. Despite large interpatient variability in the PKs of MPA, MPAG, and AcMPAG among thoracic transplant recipients, there appear to be significant differences between lung and heart patients, which warrant further study.
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There is discussion concerning the cardiac safety of citalopram in an overdose. The aim of this study was to investigate the toxic effects and toxicokinetic parameters of citalopram in an overdose as a single drug and in combination with other drugs. Cases observed between 1997 and 2006 were evaluated. ⋯ Cardiac toxicity is generally mild. Therefore, we recommend seizure precautions and intensive care unit admission with cardiac monitoring for citalopram-intoxicated patients. Because elimination half-life is prolonged, normal pharmacokinetics do not apply.
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Several studies have demonstrated the impact of CYP2D6 polymorphism on the pharmacokinetics of tramadol. However, the relationship between the O-demethylation of tramadol and O-desmethyltramadol (M1) and CYP2D6 activity has not previously been investigated with tramadol in multimedicated outpatients under steady-state conditions. Hence, the aim of this study was to determine if the well documented pharmacokinetics of tramadol regarding CYP2D6 could be verified in a study including 88 multimedicated Faroese patients, treated with tramadol at steady-state conditions. ⋯ The concentrations of (+)-M1 when corrected for dose (nM/mg) and the (+)-M1/(+)-tramadol ratio were approximately 14-fold higher in the extensive metabolizers (EMs) than in the PMs. In conclusion, the impact of the CYP2D6 polymorphism on the pharmacokinetics of tramadol was clearly demonstrated in a group of multimedicated patients treated with tramadol under steady-state conditions. Further, the frequency of PMs was not higher than that in other European populations, as previously shown in different Faroese groups, possibly because of discontinued tramadol treatment in Faroese patients who were PMs.