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Laurent Becquemont

Publications and source records attributed to Laurent Becquemont.

At least 19 recordsLinked to original sources
PubMed2006

Effects of ursodeoxycholic acid on P-glycoprotein and cytochrome P450 3A4-dependent pharmacokinetics in humans.

BACKGROUND AND OBJECTIVE: On the basis of in vitro studies indicating that ursodeoxycholic acid (UDCA) is a cytochrome P450 (CYP) 3A4 inducer and a pregnane X receptor activator and because the pregnane X receptor is a transcriptional regulator of multidrug resistance 1 (MDR1)/P-glycoprotein (P-gp), we postulated that UDCA might decrease the bioavailability of CYP3A4 and P-gp probe drugs in humans. The main objective of this study was to determine whether UDCA alters the pharmacokinetics of digoxin and midazolam. The secondary objective was to determine whether the intestinal expression of P-gp and CYP3A4 is increased by UDCA. METHODS: The effect of UDCA on MDR1 and CYP3A4 messenger ribonucleic acid (mRNA) expression was investigated in human colon carcinoma cell lines LS174T and Caco-2. Eight healthy volunteers participated in this open, nonrandomized 2-period study, in which the effects of UDCA (13 mg.kg(-1).d(-1) during 2 weeks) versus control on the pharmacokinetics of digoxin (0.5-mg single intravenous infusion), d3-digoxin (3-fold deuterated digoxin, 0.5-mg single oral dose), and midazolam (7.5-mg single oral dose) were compared. Duodenal biopsy specimens were obtained during both periods to quantify MDR1/P-gp and CYP3A4 expression. RESULTS: In vitro UDCA induced MDR1 and CYP3A4 mRNA in Caco-2 cells but not in LS174T cells. In humans UDCA significantly decreased the extent of digoxin absorption from 0.77 to 0.70 and the oral d3-digoxin area under the plasma concentration-time curve from 0 to 4 hours from 6.4 +/- 1.7 ng.h.mL(-1) to 5.3 +/- 1.5 ng.h.mL(-1) (P = .01 and P = .05, respectively). UDCA had no detectable effects on the pharmacokinetics of midazolam or the intestinal mRNA and protein expression levels of MDR1/P-gp and CYP3A4. CONCLUSION: Under the conditions in our study, UDCA only modestly decreased digoxin disposition without detectable changes in midazolam pharmacokinetics. The clinical relevance of these findings remains to be determined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Environmental and genetic factors associated with morphine response in the postoperative period.

OBJECTIVE: The aim of this study was to investigate the respective influence of genetic and nongenetic factors on morphine dose requirements and adverse effects after colorectal surgery. METHODS: Seventy-four patients who planned to undergo colorectal surgery were included in this pilot study. The cumulative 24-hour postoperative dose of morphine and postoperative nausea or vomiting requiring the antiemetic ondansetron were the 2 clinical end points. The association of patient characteristics, A118G mu-opioid receptor (OPRM1) single-nucleotide polymorphism (SNP); T802C uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7) SNP; and 2 adenosine triphosphate-binding cassette, subfamily B, member 1 (ABCB1) (multidrug resistance 1 [MDR1]) exonic SNPs (G2677T/A and C3435T) with study end points was investigated. RESULTS: Age, creatinine clearance, and the regular use of psychotropic agents were found to be significantly associated with postoperative morphine dose requirements by univariate analysis. Multivariate analysis identified that age (P = .01) and the use of psychotropic agents before surgery (P = .03) were positively associated with a higher rate of morphine consumption. A higher weight (P = .05) and the ABCB1 homozygous GG-CC diplotype (P = .03) were significantly associated with fewer morphine side effects by univariate analysis. The homozygous ABCB1 diplotype (GG-CC) conferred an odds ratio of 0.12 (95% confidence interval, 0.01-0.98) with regard to the use of ondansetron for postoperative nausea or vomiting. Multivariate analysis identified that the ABCB1 GG-CC diplotype was the only borderline-significant (P = .07) predictive factor of morphine side effects. CONCLUSION: Age and prior use of psychotropic agents are associated with postoperative morphine dose requirements. Whether ABCB1 polymorphisms might predict morphine side effects remains to be determined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Erythromycin infusion prior to endoscopy for acute upper gastrointestinal bleeding: a randomized, controlled, double-blind trial.

BACKGROUND/AIM: Presence of clots in the stomach makes emergency endoscopy difficult in patients with upper gastrointestinal bleeding. We investigated whether the association of erythromycin infusion to gastric lavage could improve stomach cleansing before endoscopy. PATIENTS AND METHODS: One hundred patients admitted for upper gastrointestinal bleeding were randomly assigned to receive either gastric lavage plus intravenous erythromycin (250 mg) or gastric lavage plus placebo before endoscopy in a double-blind study. The primary end point was the efficacy of intravenous erythromycin to improve stomach cleansing before endoscopy, assessed by both subjective and objective criteria. RESULTS: Characteristics of patients at admission were similar in both groups. Sixty-six patients had portal hypertension. The gastric mucosa was entirely visualized by the endoscopist in 65% of patients in the erythromycin group, versus 44% in the placebo group (p<0.05). The quality of examination of the upper gastrointestinal tract, assessed by using a 10-cm visual analog scale, was better in the erythromycin group (4.2+/-2 vs. 3.3+/-2.2, p<0.05). Clots were found in the stomach in 30% of patients in the erythromycin group, versus 52% in the placebo group (p<0.05). However, ability to identify the source of bleeding, mean duration of endoscopy, and need for a second-look endoscopy, did not differ between the two groups. Similar results were observed in the subgroup of cirrhotic patients. Erythromycin was well tolerated by all patients. CONCLUSION: Intravenous erythromycin before endoscopy improves stomach cleansing and quality of endoscopic examination in patients with upper gastrointestinal bleeding, but the clinical benefit is limited.

Acute Disease↗
PubMed2006

[Pharmacogenetics and interindividual variability in drug response: cytochrome P-450 2C9 and coumarin anticoagulants].

Pharmacogenetics, a discipline still in its infancy, is the study of genetically determined variations in how individuals respond to drugs. Mutations may affect drug metabolism, transmembrane transport into cells, or target receptors. Genetic polymorphisms affecting drug metabolism were the first to be identified. Genetic factors control the activity of phase I reactions involving cytochrome (CYP) P450 isoenzymes. Three CYP families catalyze drug metabolism in humans. Their genes have been identified and polymorphisms have been described in various populations, leading to either high activity ("extensive metabolizer" phenotype) or low activity ("poor metabolizer" phenotype). The CYP2C9 polymorphism illustrates the potential clinical importance of pharmacogenetics. This enzyme catalyzes the metabolism of the coumarinic oral anticoagulants acenocoumarol and warfarin. The homozygous mutant genotype CYP 2C9 *31*3, present in 0, 7% of Caucasians, leads to low enzyme activity and thus to the accumulation of these drugs in the body; this in turn increases the anticoagulant activity and induces a higher risk of bleeding. In three clinical studies of patients and healthy volunteers, we found that this CYP2C9 *3 mutant allele was responsible for 14% of the variability in the response to these drugs. Then, by studying the genetic polymorphism of the receptor site of oral anticoagulants--the vitamin K epoxide reductase multiprotein complex--we showed that a combination of the two genetic variants (CYP2C9 and the receptor site) was responsible for 50% of the variability. These data suggest that patients who have both genetic polymorphisms could be at an increased risk of bleeding during oral anticoagulant therapy.

Aryl Hydrocarbon Hydroxylases↗
PubMed2005

Absence of association between MDR1 genetic polymorphisms, indinavir pharmacokinetics and response to highly active antiretroviral therapy.

OBJECTIVE: The relationship between MDR1 single nucleotide polymorphisms (SNP) and the pharmacokinetic or pharmacodynamic responses to protease inhibitors has been recently challenged. AIM: The objective of the present study was to determine whether MDR1 genetic polymorphisms in exons 21 and 26 (G2677T/A and C3435T) are in association with indinavir (IDV) plasma concentrations and/or therapeutic response to highly active antiretroviral therapy (HAART) in HIV-infected patients treated with unboosted IDV containing regimens. METHODS: MDR1 genotyping was performed in a population of 139 HIV-1-positive patients followed during 72 weeks, as part of the previous study called ANRS 081 'Trianon'. The primary study was a randomized trial comparing over 72 weeks the efficacy of two antiretroviral drug combinations in a population of adult HIV-1-infected patients: group 1, [lamivudine (3TC) - stavudine (d4T) - IDV (800 mg three times daily)] and group 2, [Nevirapine (NVP) - d4T - IDV (1000 mg three times daily)]. RESULTS: MDR1 SNPs analyzed separately or combined into haplotypes did not show any significant association with IDV pharmacokinetics nor response to HAART. Mean modelled IDV peak and trough concentrations, as well as clearance modelled from pharmacokinetic model, after 8 weeks of therapy were not significantly different between patients carrying the wild-type haplotype GG-CC (at position 2677 and 3435 respectively) and others. CONCLUSIONS: Our results do not support an association between MDR1 genetic polymorphisms and modelled IDV clearance or clinical response to HAART.

Adult↗
PubMed2005

Measurement of CYP2D6 and CYP3A4 activity in vivo with dextromethorphan: sources of variability and predictors of adverse effects in 419 healthy subjects.

OBJECTIVE: Dextromethorphan (DEM) shares part of the adverse event profile of opioids and is widely used as a probe drug for CYP2D6 phenotyping and for the assessment of CYP2D6 activity. It has also been used to assess CYP3A4 activity. This study examined the influence of anthropometric variables, oral contraceptives, smoking habits, mu-opioid receptor and MDR1 genetic polymorphisms and components of the DEM ratios on the variability of CYP2D6 and CYP3A4 metabolic ratios and on the occurrence of adverse events following DEM administration. METHODS: This was a retrospective analysis of a database in 419 healthy subjects. CYP2D6 and CYP3A4 metabolic ratios were measured as the log of the ratios of the amount of DEM to the amount of dextrorphan (DOR) and of the amount of DEM to the amount of 3-methoxy-morphinan (MET) excreted in urine during a 12-h time period, respectively, following the oral administration of 80 mg of dextromethorphan hydrobromide. Logistic regression was performed to examine the factors associated with changes in metabolic ratios and with the occurrence of adverse events. RESULTS: The CYP2D6 metabolic ratio allowed identification of extensive and poor metabolizers of DEM. The CYP2D6 and CYP3A4 metabolic ratios were not strictly independent one from each other. Based on multivariate analysis, the CYP2D6 metabolic ratio was a stronger independent predictor of adverse events (p<0.0001) than the CYP2D6 phenotype (p=0.05). Anthropometric variables, oral contraceptives, smoking habits, mu-opioid receptor and MDR1 genetic polymorphisms did not significantly contribute to changes in metabolic ratios or to the occurrence of adverse events. CONCLUSIONS: Dextromethorphan can be used for CYP2D6 phenotyping, but the CYP2D6 and CYP3A4 metabolic ratios are not strictly independent one from each other. The CYP2D6 metabolic ratio predicts adverse events to DEM as does CYP2D6 phenotype, and extensive metabolizer subjects are not protected against adverse events.

Adult↗
PubMed2005

Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity.

The aim of the study is to explore the contribution of genetic factors related either to drug metabolism (cytochrome P450 2C9) or to drug target (vitamin K epoxide reductase) to variability in the response to acenocoumarol among 222 healthy volunteers after a single oral dose. Associations between a pharmacodynamic index (reduction in factor VII activity and international normalized ratio [INR] change) and several genetic polymorphisms (VKORC1: -4931T>C, -4451C>A, -2659G>C, -1877A>G, -1639G>A, 497C>G, 1173C>T, and CYP2C9*3) were investigated using haplotype and univariate analyses. VKORC1 haplotypes were associated with the pharmacologic response, and this association can be explained only by the effect of the -1639G>A polymorphism (or alternatively by 1173C>T, which is in complete association with it). Indeed, it explains about one third of the variability of the pharmacologic response (37% of factor VII decrease and 30% of INR change). Moreover, the previously observed effect of the CYP2C9*3 allele is independent of the VKORC1 gene effect. These 2 polymorphisms account for up to 50% of the interindividual variability. The simple genotyping of 2 single-nucleotide polymorphisms (SNPs), VKORC1 -1639G>A or 1173C>T and the CYP2C9*3 polymorphisms, could thus predict a high risk of overdose before initiation of anticoagulation with acenocoumarol, and provide a safer and more individualized anticoagulant therapy.

Acenocoumarol↗
PubMed2004

Pharmacogenetics of acenocoumarol pharmacodynamics.

OBJECTIVE: The aim of this study was to investigate the respective contribution of the different cytochrome P450 (CYP) 2C9 genetic polymorphisms to the interindividual variability of acenocoumarol pharmacodynamic response. METHODS: A total of 263 healthy volunteers were genotyped for CYP2C9*2, CYP2C9*3, CYP2C9*4, and CYP2C9*5 alleles, as well as for the nicotinamide adenine dinucleotide phosphate, reduced, quinone oxidoreductase 1 genetic polymorphism (NQO1*2). Moreover, the 5'-flanking region of the CYP2C9 gene was investigated for new polymorphisms, and haplotype analysis was then performed. Finally, CYP2C9 phenotype was evaluated after a single oral dose of 4 mg of acenocoumarol. Factor VII coagulant activity was measured before and 24 hours after acenocoumarol intake. RESULTS: The CYP2C9*3 allele was the only nonsynonymous single nucleotide polymorphism (SNP) influencing acenocoumarol pharmacodynamics; the percentages of remaining factor VII were 60% +/- 19%, 39% +/- 17%, and 17% for CYP2C9*1/CYP2C9*1, CYP2C9*1/CYP2C9*3, and CYP2C9*3/CYP2C9*3 subjects, respectively (P =.001). Among the white subjects, the CYP2C9 promoter showed the existence of 6 SNPs at positions G-1538A, T-1189C, G-1097A, G-982A, T-640 del, and G-620T with allelic frequencies of 0.085, 0.0398, 0.136, 0.086, 0.005, and 0.0138, respectively. Four major haplotypes could be inferred among white subjects. The haplotype that contains the CYP2C9*3 allele was the only one influencing acenocoumarol pharmacodynamics, explaining 14.3% of its interindividual variability. Body weight explained 5% of acenocoumarol pharmacodynamic variability, whereas the NQO1*2 allele had no significant effect. CONCLUSION: Overall, CYP2C9-related genetic variability accounts for 14% of the interindividual variability in acenocoumarol pharmacodynamic response. The information found by haplotype analysis is mainly related to the CYP2C9*3 SNP.

Acenocoumarol↗
PubMed2003

Digoxin pharmacokinetics and MDR1 genetic polymorphisms.

BACKGROUND: The effect of MDR1 C3435T single nucleotide polymorphism (SNP) in exon 26 on digoxin pharmacokinetics has recently been challenged. OBJECTIVE. To clarify the relationships between MDR1 genetic polymorphisms in exon 26 (C3435T) and 21 (G2677T/A) and digoxin pharmacokinetics. MATERIALS AND METHODS: MDR1 genotypes for C3435T and G2677T/A SNPs were determined in 32 healthy subjects whose single oral dose digoxin pharmacokinetics had been measured over 48 h. RESULTS: A significant relationship was observed between C3435T SNP and digoxin AUCs ( p<0,05). Homozygous TT subjects had 20% higher digoxin plasma concentrations than CT and CC subjects and a trend for higher 48 h digoxin urinary recoveries (TT>CT>CC). Similar results, although not statistically significant, were observed from the MDR1 G2677T/A SNP. CONCLUSIONS: Our results confirm that the MDR1 C3435T single nucleotide polymorphism (SNP) significantly affects digoxin disposition kinetics, with homozygous TT subjects presenting the highest plasma concentrations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Frequency of cytochrome P450 2C9 allelic variants in the Chinese and French populations.

Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the metabolism of different drugs with low therapeutic index such as oral anticoagulants. CYP2C9*2 and CYP2C9*3 are two single nucleotide polymorphic allelic variants. The frequency of these alleles in different ethnic populations is extremely variable. In this study, we compared the frequencies of CYP2C9 allelic variants among 394 Chinese living in Shanghai to 151 French Caucasians living in Paris. The allelic frequencies of CYP2C9 variants of the Chinese and the French subjects were 0.963, 0.001, 0.036 and 0.77, 0.15, 0.08 for CYP2C9*1, CYP2C9*2, CYP2C9*3, respectively. Chinese CYP2C9*3 allelic frequency was twice as lower as the French subjects, but three times higher than Korean (0.036 vs. 0.011). The CYP2C9*2 allele could be detected in only one Chinese subject, whereas it represented the major allelic variant in French Caucasians. The low frequency of the CYP2C9*2 and CYP2C9*3 allelic variants in Chinese subjects does not justify their detection in clinical practice, unlike French Caucasians.

Adolescent↗
PubMed2003

Dipyridamole enhances digoxin bioavailability via P-glycoprotein inhibition.

BACKGROUND: On the basis of in vitro studies indicating that dipyridamole is an inhibitor for the MDR1 efflux membrane transporter P-glycoprotein, we postulated that dipyridamole could increase the bioavailability of digoxin, a P-glycoprotein substrate. OBJECTIVES: The main objective was to determine whether dipyridamole alters the bioavailability of digoxin. The secondary objective was to determine whether the magnitude of the pharmacokinetic interaction was influenced by MDR1 genetic polymorphism in exon 26 (C3435T). MATERIAL AND METHODS: (1) The effect of dipyridamole on in vitro P-glycoprotein-mediated, polarized transport of tritium-labeled digoxin was investigated in Caco-2 cell monolayers. (2) Twelve healthy volunteers participated in this open, randomized, 2-period crossover study, in which the effects of dipyridamole (300 mg/d for 3 days) versus placebo on the pharmacokinetics of a single oral dose of digoxin (0.5 mg) were compared. MDR1 genotyping (exon 26, C3435T) was determined before the study to include 6 homozygous CC and 6 homozygous TT subjects. RESULTS: Dipyridamole inhibited [(3)H]digoxin transport in Caco-2 cells with a 50% inhibitory concentration value of 1.5 +/- 1.5 micromol/L. We observed a 20% and 13% increase in digoxin area under the plasma concentration-time curve (AUC) from 0 to 4 hours and AUC from 0 to 24 hours (P <.05), respectively, during dipyridamole administration, which was consecutive to an increase in digoxin absorption. Digoxin AUC from 0 to 4 hours and AUC from 0 to 24 hours were significantly higher among subjects harboring the TT compared with the CC MDR1 genotype: 7.5 +/- 1.2 ng x h x mL(-1) versus 6.1 +/- 0.8 ng x h x mL(-1) and 20.2 +/- 2.1 ng x h x mL(-1) versus 16.8 +/- 1.7 ng x h x mL(-1), respectively (P <.05). Digoxin pharmacokinetic modifications during the dipyridamole period were similar in both genotypes. CONCLUSION: Dipyridamole is an in vitro and in vivo P-glycoprotein inhibitor that increases intestinal digoxin absorption and digoxin plasma concentrations. In light of the modest changes in digoxin pharmacokinetics in the presence of dipyridamole, this drug interaction is probably clinically irrelevant.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Clinical relevance of pharmacogenetics.

Pharmacogenetics fields of research was initially restricted to drug metabolism enzymes. It has recently progressed to drug transporters, receptors, and any kind of targets that can modulate drug response. This rapid extension of pharmacogenetics to all the different medical specialties is in close relation with the recent completion of the draft sequence of the human genome and the discovery that about 0.1% of its sequence is polymorphic. The goal of pharmacogenetics for the next years is clearly to determine the clinical consequences of these 2-3 million single nucleotide polymorphisms (SNPs). Things can be schematically divided in two situations. (1) Frequent SNPs (allele frequency > 10%) which have a low impact on drug response (odds ratios < 2), even combined with other SNPs in haplotype combinations. Such situations, which are by far the most frequent, have no clinical relevance for a single patient to predict its response to a particular drug. CYP3A and MDR1 allelic variants are good examples of such frequent situations. (2) Rare SNPs, which dramatically alter the expression or the activity of a target protein, can sometimes have a real clinical relevance (odds ratios > 5), usually to predict drug side effects. Only few examples, such as TPMT and CYP2C9 genetic polymorphisms, can illustrate this rare situation. Unfortunately, less than 1% of the population is concerned by these rare SNPs, and genotyping can only explain a small part of the variability of the response to a single drug. Beside the impressive mass of data available for pharmacogenetics, it is surprising to observe its poor development in routine medical practice. This discrepancy relies mainly on educational and methodological problems, which might be solved in the decade. To promote pharmacogenetics in routine medical practice, large prospective randomized trials are needed to demonstrate that pharmacogenetic orientated prescription can sometimes predict drug response without dramatic increase in costs.

Animals↗
PubMed2003

Association of the multidrug resistance-1 gene single-nucleotide polymorphisms with the tacrolimus dose requirements in renal transplant recipients.

The immunosuppressive drug tacrolimus, whose pharmacokinetic characteristics display large interindividual variations, is a substrate for P-glycoprotein (P-gp), the product of the multidrug resistance-1 (MDR1) gene. Some of the single nucleotide polymorphisms (SNP) of MDR1 reported correlated with the in vivo activity of P-gp. Because P-gp is known to control tacrolimus intestinal absorption, it was postulated that these polymorphisms are associated with tacrolimus pharmacokinetic variations in renal transplant recipients. The objective of this study was to evaluate in a retrospective study of 81 renal transplant recipients the effect on tacrolimus dosages and concentration/dose ratio of four frequent MDR1 SNP possibly associated with P-gp function (T-129C in exon 1b, 1236C>T in exon 12, 2677G>T,A in exon 21, and 3435C>T in exon 26). As in the general population, the SNP in exons 12, 21, and 26 were frequent (16, 17.3, and 22.2% for the variant homozygous genotype, respectively) and exhibited incomplete linkage disequilibrium. One month after tacrolimus introduction, exon 21 SNP correlated significantly with the daily tacrolimus dose (P < or = 0.05) and the concentration/dose ratio (P < or = 0.02). Tacrolimus dose requirements were 40% higher in homozygous than wild-type patients for this SNP. The concentration/dose ratio was 36% lower in the wild-type patients, suggesting that, for a given dose, their tacrolimus blood concentration is lower. Haplotype analysis substantiated these results and suggested that exons 26 and 21 SNP may be associated with tacrolimus dose requirements. Genotype monitoring of the MDR1 gene reliably predicts the optimal dose of tacrolimus in renal transplant recipients and may predict the initial daily dose needed by individual patients to obtain adequate immunosuppression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Effect of interferon alpha-ribavirin bitherapy on cytochrome P450 1A2 and 2D6 and N-acetyltransferase-2 activities in patients with chronic active hepatitis C.

BACKGROUND: Interferon alpha (IFN-alpha) is thought to be responsible for cytochrome P450 (CYP)-dependent drug interactions mediated by a decrease in CYP activities. OBJECTIVES: The objectives are to determine whether IFN-alpha and ribavirin can alter pretreatment CYP1A2, CYP2D6, CYP3A4 and N-acetyltransferase-2 activities after 1 month of treatment. METHODS: Enzymatic activities were determined among 14 patients with chronic active hepatitis C before IFN-alpha (3. 10(6) U, 3 times a week) and ribavirin introduction and after 1 month of treatment. During both study periods, subjects received 80 mg dextromethorphan and 140 mg caffeine (1,3,7-trimethylxanthine [137X]). CYP3A4, CYP2D6, and NAT2 activities were assessed by use of urinary metabolic ratios of 3-methoxymorphinan/dextromethorphan, dextrorphan/dextromethorphan, and 5-acetylamino-6-formylamino-3-methyluracil (AFMU)/1-methylxanthine(1X). The plasma paraxanthine/caffeine ratio was used to measure CYP1A2 activity. RESULTS: CYP3A4 and CYP2D6 activities tended to increase after 1 month of antiviral therapy, but the change did not reach statistical significance. CYP1A2 and NAT2 activities were not significantly modified after 1 month of antiviral treatment. Pretreatment activities were significantly lower than those previously observed in healthy volunteers for CYP2D6 (mean +/- SD, 148 +/- 139 versus 759 +/- 692; P =.0008) and CYP3A4 (0.18 +/- 0.06 versus 0.52 +/- 0.72; P =.0006). This difference was no longer statistically significant after 1 month of treatment, because CYP2D6 and CYP3A4 activities improved in 7 patients. CONCLUSION: In patients with chronic hepatitis C, pretreatment CYP3A4 and CYP2D6 activities were significantly lower than those observed in healthy volunteers. These differences disappeared after 1 month of antiviral treatment because of the restoration of these CYP activities in about half of the patients.

Acute Disease↗