Biomedical subjects

R Marchiselli

Publications and source records attributed to R Marchiselli.

4 recordsLinked to original sources

PubMed1997

A rapid and specific assay for the determination of lamotrigine in human plasma by normal-phase HPLC.

A rapid and specific high-performance liquid chromatography assay of lamotrigine in human plasma is described. Lamotrigine is extracted with dichloromethane from buffered plasma to which an internal standard has been added. The solvent is directly injected into a 250 x 4.6-mm Spherisorb Silica column and the drug is eluted by using a mixture of methanol, n-heptane, dichloromethane, and 28-30% ammonium hydroxide (20:40:40:0.3 vol/vol) at a flow rate of 1 ml/min. The eluates are detected at 240 nm. The assay requires 250 microliters of sample, and concentrations as low as 0.4 microgram/ml can be measured accurately. The method is linear in the range of 0.4-16 micrograms/ml, with a mean coefficient of correlation (r) > or = 0.997. Within- and between-day relative standard deviations at three different concentration levels (1, 4, and 8 micrograms/ml) are < or = 8.6%.

Anticonvulsants↗

PubMed1996

Effect of enzyme inducing anticonvulsants on ethosuximide pharmacokinetics in epileptic patients.

1. To assess the effect of enzyme inducing anticonvulsants on ethosuximide pharmacokinetics, plasma ethosuximide concentrations after a single oral dose (500 mg) of the drug were compared in 12 healthy control subjects and 10 epileptic patients receiving chronic therapy with phenobarbitone, phenytoin and/or carbamazepine. 2. Compared with controls, epileptic patients showed markedly shorter ethosuximide half-lives (29.0 +/- 7.8 vs 53.7 +/- 14.3 h, means +/- s.d., P < 0.001) and higher apparent oral clearance (CL/F) values (15.3 +/- 3.8 vs 9.2 +/- 1.9 ml kg-1 h-1, P < 0.001). The apparent volume of distribution (V/F) of ethosuximide was slightly lower in the patients than in controls (0.6 +/- 0.1 vs 0.7 +/- 0.1 l kg-1, P < 0.05). 3. These findings provide evidence that ethosuximide elimination is increased by enzyme inducing anticonvulsants, the effect probably being mediated by stimulation of cytochrome CYP3A activity. 4. The enhancement of ethosuximide clearance in patients comedicated with enzyme inducing anticonvulsants is likely to be clinically relevant. Higher ethosuximide dosages will be required to achieve therapeutic drug concentrations in these patients.

Adult↗

PubMed1996

The influence of ethnic factors and gender on CYP1A2-mediated drug disposition: a comparative study in Caucasian and Chinese subjects using phenacetin as a marker substrate.

To assess potential ethnic and gender-related differences in the expression of cytochrome CYP1A2-mediated activity, the pharmacokinetics of phenacetin (a CYP1A2 substrate) and its metabolite paracetamol were compared in 20 Caucasian and 20 Chinese subjects after administration of a single oral 900 mg phenacetin dose. Peak plasma concentrations and apparent oral clearance values for phenacetin did not differ between the two groups (geometric means: 3.4 micrograms/ml and 1.56 ml h-1 kg-1, respectively, for Caucasians vs. 4.7 micrograms/ml and 1.25 ml h-1 kg-1, respectively, for Chinese, after excluding one Caucasian with aberrantly low plasma phenacetin values). Pharmacokinetic parameters for metabolically derived paracetamol were also similar in the two groups. When subjects were divided into subgroups according to gender, phenacetin apparent oral clearance values were found to be lower in Chinese women compared with both Chinese men and Caucasian subjects of either sex. It is concluded that there are no major interethnic differences in the expression of CYP1A2-related activity between Caucasians and Chinese, although Chinese women as a subgroup may exhibit comparatively lower enzyme activity.

Acetaminophen↗

PubMed1993

Vigabatrin-induced decrease in serum phenytoin concentration does not involve a change in phenytoin bioavailability.

The possibility that vigabatrin (VGB) decreases serum phenytoin (PHT) concentration by lowering the oral bioavailability of PHT was investigated in 21 patients with epilepsy. Each patient was switched from oral to intravenous PHT for 5 days before and after combined treatment with VGB. After VGB (2-3.5 g day(-1) for at least 5 weeks), serum PHT concentrations decreased slightly from 87 +/- 25 to 76 +/- 31 micromol l(-1) (means +/- s.d., P < 0.05), but in a subgroup of seven patients the decrease was more prominent (from 72 +/- 22 to 49 +/- 17 micromol l(-1), P < 0.005). At baseline (before VGB), serum PHT remained unaffected (85 +/- 30 micromol l(-1)) after switching PHT dosage to the intravenous route, indicating that the oral availability of the drug was virtually complete. During VGB treatment, serum PHT was also unchanged (74 +/- 34 micromol l(-1)) after switching from oral to intravenous therapy, and this was also true for the subgroup of patients showing a prominent interaction (48 +/- 18 micromol l(-1)). The urinary recoveries of PHT and its metabolites pHPPH and mHPPH remained constant throughout the study. It is concluded that the oral availability of PHT is unaffected by VGB and that the VBG-induced decrease in serum PHT is mediated by alternative mechanisms.

Adolescent↗