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Biomedical subjects

R Dahlqvist

Publications and source records attributed to R Dahlqvist.

At least 19 recordsLinked to original sources
PubMed2001

Incorrect use and limited weight reduction of orlistat (Xenical) in clinical practice. A cohort study.

OBJECTIVE: To study the prescribing of the antiobesity drug orlistat in relation to the approved indication and its weight-reducing effect in clinical practice during the first 3 months of treatment. METHODS: Anonymous postal questionnaire survey to prescribers of orlistat concerning a random sample of 1000 of 20,000 prescriptions. PARTICIPANTS: Useful information was obtained for 789 patients. SETTING: Primary and secondary care in Sweden. MAIN OUTCOME MEASURES: Beginning and continued treatment according to the approved indication. Dropout from treatment. Weight loss during treatment. RESULTS: Four percent of the patients were prescribed orlistat despite having a body mass index (BMI) less than 28 kg/m2. Only 24% of the patients had a diet period with a weight loss of 2.5 kg or greater before the start of therapy. Half of the patients with a weight loss of less than 5% after 3 months continued the treatment. Ten percent gained weight or had no weight loss at all while 43% lost less than 5% in weight. At least one-quarter of the patients stopped the treatment within the observation period. CONCLUSION: Orlistat was not prescribed according to the approved indication in the majority of cases. The dropout rate was high and most patients had minor gain from the treatment.

Adult↗
PubMed2001

Olanzapine disposition in humans is unrelated to CYP1A2 and CYP2D6 phenotypes.

OBJECTIVE: Limited data suggest that CYP1A2 and CYP2D6 are involved in the metabolism of olanzapine. The purpose of this study was to further elucidate the role of these enzymes in the disposition of olanzapine in vivo. METHODS: Seventeen healthy non-smoking male volunteers were included in the study. Five subjects were CYP2D6 poor metabolisers (PMs), and 12 were CYP2D6 extensive metabolisers (EMs). All subjects received a single oral dose of 7.5 mg olanzapine, and serum concentrations were measured for 96 h using gas chromatography. A cross-over study was undertaken in the 12 CYP2D6 EMs who at least 2 weeks before or after the olanzapine dose received a single oral dose of 200 mg caffeine. The concentrations of caffeine and paraxanthine were measured in saliva 10 h after caffeine intake, and the paraxanthine/caffeine ratio was calculated as a measure of CYPIA2 activity. RESULTS: A threefold inter-individual variability in oral clearance (CLoral) and maximum serum concentration (Cmax) of olanzapine was observed and a 2.3-fold inter-individual variability in CYPIA2 activity. There was no significant correlation between CYP1A2 activity and oral clearance of olanzapine (r=-0.19, P=0.56). Moreover, there were no significant differences in any of the olanzapine pharmacokinetic parameters between the CYP2D6 PMs and EMs (CLoral=0.246 l h(-1) kg(-1) and 0.203 l h(-1) kg(-1), respectively, P=0.30). CONCLUSION: Neither CYP1A2 nor CYP2D6 seem to have a dominating role in olanzapine biotransformation after intake of a single dose.

Adult↗
PubMed2001

The major fluvoxamine metabolite in urine is formed by CYP2D6.

OBJECTIVE: Previous studies have shown that fluvoxamine is metabolized by CYP1A2 and CYP2D6, but there is no information on the impact the various CYP enzymes have on the different metabolic pathways of fluvoxamine biotransformation. The present study was designed to investigate this issue. METHODS: The major fluvoxamine metabolite, the 5-demethoxylated carboxylic acid metabolite, was analyzed in urine from 50 healthy volunteers after intake of a single oral dose of 50 mg fluvoxamine, and the formation clearance for the metabolite (CLm) was calculated. Of the subjects, 28 were non-smoking CYP2D6 and CYP2C19 extensive metabolizers (EMs), 12 were smokers and were thus considered to have an induced CYP1A2 activity, 5 were CYP2D6 poor metabolizers (PMs), and 5 were CYP2C19 PMs. In 11 of the non-smoking EMs, 200 mg caffeine was given at another occasion in order to calculate oral caffeine clearance as a measure of CYP1A2 activity. In addition, CLm was calculated in ten other subjects given increasing doses of fluvoxamine for 4 weeks. RESULTS: Oral clearance of fluvoxamine was significantly higher in smokers, and significantly lower in CYP2D6 PMs than in non-smoking EMs. CLm was 78% lower in CYP2D6 PMs than in the EMs. Smoking and being a CYP2C19 PM did not influence CLm. There was no significant correlation between oral caffeine clearance and CLm. CLm decreased with increasing fluvoxamine dosage, but the decrease in oral clearance was even higher. CONCLUSION: These results indicate that CYP2D6 catalyzes the major metabolic pathway of fluvoxamine, whereas CYP1A2 seems to catalyze other less important pathways. Both the CYP2D6 and the CYP1A2 pathways seem to be saturated in parallel with increasing fluvoxamine dosage.

Adult↗
PubMed2001

Influence of gender and oral contraceptives on CYP2D6 and CYP2C19 activity in healthy volunteers.

AIMS: The study was carried out in order to assess the effects of gender and the use of oral contraceptives (OCs) on CYP2D6 and CYP2C19 activities in healthy volunteers. METHODS: Six hundred and eleven Caucasian volunteers (330 males and 281 females; age range 18-49 years) were phenotyped with respect to CYP2D6 and CYP2C19 by means of the probe drugs dextromethorphan and mephenytoin, respectively. Extensive metabolisers were selected for this study. RESULTS: The median dextromethorphan/dextrorphan metabolic ratio in non-OC using females was significantly lower than in males (0.067 vs 0.080; P = 0.033) (mean difference in ln dextromethorphan/dextrorphan metabolic ratio 0.023, 95% CI 0.03-0.43). For the mephenytoin S/R ratio, no such difference was observed. However, OC using females had a significantly higher median mephenytoin S/R ratio than non-OC using females (0.230 vs 0.090; P < 0.001) (mean difference in ln mephenytoin S/R ratio 0.082, 95% CI 0.60-1.04). Moreover, females using combined OCs had a significantly higher median ratio than females using OCs with progestins only (median 0.258 vs 0.135; P = 0.008) (mean difference in ln mephenytoin S/R ratio 0.82, 95% CI 0.21-1.34). CONCLUSIONS: Given certain assumptions, the study indicates that females in the fertile age have a slightly higher CYP2D6 activity compared with males. There was no evidence of a gender difference in CYP2C19 activity. The use of combined OCs reduces the activity of CYP2C19, an effect that seems to be related to the ethinyloestradiol component.

Adolescent↗
PubMed2000

Attitudes to reporting adverse drug reactions in northern Sweden.

OBJECTIVES: This study was designed to investigate attitudes of general practitioners (GPs) and hospital physicians in Sweden towards spontaneous reporting of adverse drug reactions (ADRs). METHOD: Two areas in the northern region of Sweden were selected for the study. A knowledge and attitude questionnaire followed by a reminder letter 2 weeks later was addressed to all GPs and hospital physicians in the study areas. RESULT: The total response rate from the study areas was 748 of the 1274 questionnaires sent out (58.7%). Of those who responded, 236 were GPs, 433 were hospital physicians and 79 had other positions. Of the responders, 252 stated that they had never reported any ADR and 488 that they had reported at least once in their career. Issues that came out as important in the decision to report or not to report were whether the reaction was considered well-known or not, the severity of the reaction, hesitance to report only on suspicion, lack of knowledge of existing rules, giving priority to other matters and lack of time to report ADRs. Only minor differences in these regards were observed between male and female physicians. CONCLUSION: Our investigation shows that the physicians in northern Sweden have a fairly good knowledge about the existing rules for reporting ADRs in Sweden. However, the attitudes leave room for considerable under-reporting due to matters related mainly to the medical impact of the reaction and of reporting it, but also to the scientific "paradox" of reporting only on suspicion and of course due to lack of time in the health care setting.

Adult↗
PubMed2000

Citalopram pharmacokinetics in patients with chronic renal failure and the effect of haemodialysis.

OBJECTIVE: To study the effects of severe renal failure and haemodialysis on the pharmacokinetics of citalopram. METHODS: Four patients with renal failure undergoing haemodialysis and eight healthy controls were given a single dose of citalopram. The concentrations of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were measured in serum and urine. On a different day, the four patients undergoing haemodialysis were given another single dose of citalopram, and the drug concentrations were measured in serum from the artery leading to the dialyser and in the dialysate. In addition, one anuric patient treated with citalopram on a regular basis was included in the study. RESULTS: There were no significant differences between the two groups in any of the pharmacokinetic parameters with the exception of the renal clearance of citalopram, which was significantly lower in the renal failure group than in the control group (1.70 ml/min versus 66.2 ml/min, P<0.001). Oral clearance of citalopram was almost identical in the two groups (452 ml/min versus 456 ml/min). The process of haemodialysis cleared about 1% of the dose as citalopram and 1% as desmethylcitalopram only. CONCLUSION: Severe renal failure does not affect the pharmacokinetics of citalopram and modification of the usual citalopram dose does thus not seem to be necessary. The contribution of haemodialysis to the total elimination of citalopram is negligible.

Adult↗
PubMed2000

Effect of caffeine on clozapine pharmacokinetics in healthy volunteers.

AIMS: To assess the effects of caffeine on the pharmacokinetics of clozapine in healthy volunteers. METHODS: This was an open label randomized crossover study in 12 nonsmoking healthy male volunteers. The subjects received a single oral dose of 12.5 mg clozapine in each phase with or without concomitant intake of caffeine (mean dose: 550 mg day-1, range: 400-1000 mg day-1 ). Serum concentrations of clozapine and its metabolites desmethyl-clozapine and clozapine-N-oxide were measured during a 48 h period in each phase. In addition, serum concentrations of caffeine and the metabolite paraxanthine were monitored. RESULTS: A 19% increase in mean clozapine AUC(0,infinity) (P=0.05) and a 14% decrease of mean oral clearance of clozapine were observed during concomitant intake of caffeine (P=0.05) compared with intake of only clozapine. Statistically significant decreases of mean ratios between AUC(0, 12h) for desmethyl-clozapine and AUC(0,12h) for clozapine (-18%), and between AUC(0,12h) for clozapine-N-oxide and AUC(0,12h) for clozapine (-23%) were observed during the caffeine phase (P=0.03 and 0.02, respectively). Oral clearance of clozapine and the ratio AUC(0, 12h) for desmethyl-clozapine/AUC(0,12h) for clozapine were correlated with the paraxanthine/caffeine ratio in serum after intake of caffeine (rs=0.62; P=0.03 and rs=0.77; P=0.003, respectively). CONCLUSIONS: These results suggest that caffeine in daily doses of 400-1000 mg inhibits the metabolism of clozapine to an extent that might be clinically significant in certain individuals.

Adult↗
PubMed2000

HMG-CoA reductase inhibitors and myotoxicity.

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors specifically inhibit HMG-CoA reductase in the liver, thereby inhibiting the biosynthesis of cholesterol. These drugs significantly reduce plasma cholesterol level and long term treatment reduces morbidity and mortality associated with coronary heart disease. The tolerability of these drugs during long term administration is an important issue. Adverse reactions involving skeletal muscle are not uncommon, and sometimes serious adverse reactions involving skeletal muscle such as myopathy and rhabdomyolysis may occur, requiring discontinuation of the drug. Occasionally, arthralgia, alone or in association with myalgia, has been reported. In this article we review scientific data provided via Medline, adverse drug reaction case reports from the Swedish Drug Information System (SWEDIS) and the World Health Organization's International Drug Information System (INTDIS) database, focusing on HMG-CoA reductase inhibitor-related musculoskeletal system events. Cytochrome P450 (CYP) 3A4 is the main isoenzyme involved in the metabolic transformation of HMG-CoA reductase inhibitors. Individuals with both low hepatic and low gastrointestinal tract levels of CYP3A4 expression may be at in increased risk of myotoxicity due to potentially higher HMG-CoA reductase inhibitor plasma concentrations. The reported incidence of myotoxic reactions in patients treated with this drug class varies from 1 to 7% and varies between different agents. The risk of these serious adverse reactions is dose-dependent and may increase when HMG-CoA reductase inhibitors are prescribed concomitantly with drugs that inhibit their metabolism, such as itraconazole, cyclosporin, erythromycin and nefazodone. Electrolyte disturbances, infections, major trauma, hypoxia as well as drugs of abuse may increase the risk of myotoxicity. It is important that the potentially serious adverse reactions are recognised and correctly diagnosed so that the HMG-CoA reductase inhibitor may at once be withdrawn to prevent further muscular damage.

Animals↗
PubMed1999

Lack of correlation between fluvoxamine clearance and CYP1A2 activity as measured by systemic caffeine clearance.

OBJECTIVE: Evidence exists to suggest that fluvoxamine is metabolized by CYP1A2. The present study was undertaken in order to further elucidate the role of CYPIA2 in fluvoxamine disposition. METHODS: Twelve healthy non-smoking male volunteers participated in this cross-over study. Six subjects received first fluvoxamine 50 mg as a single oral dose and, some weeks later, caffeine 200 mg as a single oral dose. The other six subjects received the drugs in reverse order. Serum concentrations of fluvoxamine, caffeine and paraxanthine were measured and standard pharmacokinetic parameters were calculated. RESULTS: There were no significant correlations between caffeine clearance and fluvoxamine oral clearance (rs = -0.30; P = 0.43) or between the paraxanthine/caffeine ratio in serum 6 h after caffeine intake and fluvoxamine oral clearance (rs = -0.18; P = 0.58). CONCLUSION: CYP1A2 does not appear to be of major importance in the metabolism of fluvoxamine.

Caffeine↗
PubMed1999

Absence of interaction between erythromycin and a single dose of clozapine.

OBJECTIVE: To study the suggested pharmacokinetic interaction between erythromycin, a strong inhibitor of CYP3A4, and clozapine. METHODS: Twelve healthy male volunteers received a single dose of 12.5 mg of clozapine alone or in combination with a daily dose of 1500 mg erythromycin in a randomised crossover study. Clozapine and its metabolites clozapine-N-oxide and desmethyl-clozapine were measured in serum samples which were collected during a 48 h period and in a sample of the urine secreted over the interval 0-12 h. RESULTS: There were no significant differences in mean area under the serum concentration time curves (1348 (633) nmol h x l(-1) in the control phase and 1180 (659) nmol h x l(-1) in the erythromycin phase), terminal halflives (19 (13) h and 15 (6) h, respectively), peak serum concentrations (92 (53) nmol x l(-1) and 77 (40) nmol x l(-1), respectively), time to peak serum concentrations (1.4 (0.7) h and 1.5 (1.0) h, respectively) or apparent oral clearances of clozapine (34 (15) l x h(-1) and 46 (37) l x h(-1), respectively). There were no significant differences in partial metabolic clearances to clozapine-N-oxide (5.1 (3.6) l x h(-1) and 7.8 (9.4) l x h(-1), respectively) or to desmethyl-clozapine (1.5 (1.3) l x h(-1) and 1.8 (1.7) l x h(-1), respectively) or in renal clearances of clozapine (0.8 (0.5) l x h(-1) and 1.0 (0.7) l x h(-1), respectively) between the two phases. CONCLUSION: These results demonstrate that erythromycin at a clinically relevant dosage does not inhibit the metabolism of clozapine. Hence, CYP3A4 seems to be of minor importance in the disposition of clozapine in humans at least when clozapine is taken at a low single dose.

Adult↗
PubMed1998

Non-linear fluvoxamine disposition.

AIMS: To study the pharmacokinetics of fluvoxamine when given in increasing doses to healthy volunteers. METHODS: Ten healthy, non-smoking men were given maintenance treatment with fluvoxamine for 4 weeks. Eight subjects were CYP2D6 extensive metabolisers (EMs) and two were CYP2D6 poor metabolisers (PMs). As a measure of the CYP1A2 phenotype, the paraxanthine/caffeine ratio in saliva after intake of caffeine was studied. The fluvoxamine doses given were 25 mg day(-1) the first week, 50 mg day(-1) the second week, 100 mg day(-1) the third week and 200 mg day(-1) the fourth week, divided in two daily doses. On the seventh day every week, serum concentrations of fluvoxamine were followed for a dose interval of 12 h. After discontinuation of treatment, fluvoxamine concentrations were followed for 1 week. RESULTS: For each of the three two-fold increases in given dose, the mean AUC increased 3.25-fold, 3.17-fold and 3.14-fold, respectively (P < 0.0001), indicating a decrease in oral clearance with increasing dose. The elimination half-life based upon the serum concentrations 12-48 h after discontinuation of fluvoxamine was 32.1 +/- 11.0 h whereas the half-life based upon the concentrations 3-7 days after discontinuation was significantly shorter, 15.8 +/- 4.2h (means +/- s.d.; P < 0.001). There were no significant correlations between the CYP1A2 phenotype and fluvoxamine AUCs at different doses (r = -0.56; P = 0.095 for the correlation between the paraxanthine/caffeine ratio in saliva and fluvoxamine AUC at a dose of 50 mg day[-1]). The two CYP2D6 PMs had AUC values in the same range as the EMs. CONCLUSIONS: The present study conclusively demonstrates that fluvoxamine exhibits non-linear kinetics within the therapeutic dose interval. The reason for non-linearity is not Michaelis-Menten saturation kinetics of a single metabolic pathway, but rather a complex involvement of multiple parallel pathways.

Adult↗
PubMed1998

Prevalence of diabetes and impaired glucose tolerance in patients treated with clozapine compared with patients treated with conventional depot neuroleptic medications.

BACKGROUND: Recent case reports suggest the association of the emergence of diabetes mellitus with clozapine treatment, although conventional neuroleptics have also been implicated. This study was conducted to determine if there is an increased risk of diabetes mellitus and/or impaired glucose tolerance (IGT) during clozapine treatment compared with treatment with conventional depot neuroleptics. METHOD: In a district hospital in northern Sweden, blood glucose tests and, if necessary an oral glucose tolerance test were used to assess the prevalence of diabetes mellitus or IGT in 63 patients treated with clozapine compared with 67 patients treated with conventional depot neuroleptics (haloperidol, zuclopenthixol, fluphenazine, perphenazine, or flupenthixol). Diabetes mellitus and impaired glucose tolerance were classified according to World Health Organization criteria. RESULTS: There were 3 dropouts in the clozapine group and 4 in the control group. Of subjects treated with clozapine, 12% (7/60) had type 2 diabetes mellitus, and 10% (6/60) had IGT. Of subjects treated with depot injections of neuroleptics, 6% (4/63) had type 2 diabetes mellitus and 3% (2/63) had IGT. None in either group had type 1 diabetes mellitus. Subjects in the clozapine group were significantly (p < .001) younger than subjects in the control group, whereas the 2 groups did not differ with respect to body weight, body mass index, or prevalence of diabetes mellitus in first-degree relatives. CONCLUSION: Subjects treated with clozapine were more often classified as having type 2 diabetes mellitus or IGT compared with subjects in the control group. This difference did not, however, achieve statistical significance (p=.06).

Adult↗
PubMed1997

Relationship between fluvoxamine pharmacokinetics and CYP2D6/CYP2C19 phenotype polymorphisms.

OBJECTIVE: The purpose of this study was to investigate whether the disposition of fluvoxamine is associated with the CYP2D6 and CYP2C19 phenotype polymorphisms. METHODS: The serum concentration of fluvoxamine was followed for 48 h after oral administration of a single dose of 50 mg fluvoxamine to five poor metabolizers of the CYP2D6 test drug dextromethorphan, five poor metabolizers of the CYP2C19 test drug mephenytoin, and five extensive metabolizers of both test drugs. RESULTS: Poor metabolizers of dextromethorphan had significantly higher areas under the serum concentration-time curve than extensive metabolizers of dextromethorphan (mean 1.31 vs 1.00 mumol.h.l-1). There were no differences between poor and extensive metabolizers of mephenytoin (mean, 1.00 vs 1.15 mumol.h.l-1). CONCLUSION: The results are consistent with a possible minor to moderate role of CYP2D6, but not CYP2C19, in fluvoxamine metabolism.

Adult↗
PubMed1997

Urinary excretion of codeine, ethylmorphine, and their metabolites: relation to the CYP2D6 activity.

The formation of morphine from codeine and ethylmorphine is mainly mediated by the polymorphic enzyme CYP2D6. The objective of this study was to investigate whether CYP2D6 poor metabolizers (PM) and CYP2D6 extensive metabolizers (EM) would respond differently during testing for opiate drugs of abuse in urine after intake of these drugs. Five PM and five EM of dextromethorphan were administered single oral doses of codeine (25 mg) and ethylmorphine (25 mg), and the urinary excretion of parent compounds and selected metabolites was observed for 72 hours. Analysis was performed with GC-MS after hydrolysis of the glucuronide conjugates. Selected urine samples were screened for the presence of opiates by the Abbott ADx immunoassay method. The results from one PM and one EM were excluded because of technical analytical problems. EM excreted significantly more morphine than PM after intake of both codeine (6.5% vs. 1.1% of the dose; p < 0.05) and ethylmorphine (11.0% vs. 3.0% of the dose; p < 0.05). Screening results were positive significantly longer for EM than for PM after codeine intake (mean, 33 hours vs. 17 hours; p < 0.05), and the same trend, albeit nonsignificantly, was noted for ethylmorphine (mean, 33 hours vs. 24 hours). Regardless of CYP2D6 phenotype, significantly more morphine was formed after intake of ethylmorphine than after intake of codeine (7.0% vs. 3.8% of the dose; p < 0.05). There were high correlations between dextromethorphan metabolic ratios and the ratios of codeine to morphine, ethylmorphine to morphine, norcodeine to normorphine, and norethylmorphine to normorphine (r = 0.80 to 0.92; p = 0.030 to 0.001). Although this study should be interpreted with caution because of the few subjects included and the single-dose design, it demonstrates that the CYP2D6 phenotype clearly affects the results when testing for opiates in urine after intake of codeine and ethylmorphine.

Adult↗
PubMed1997

Seizures and myoclonus associated with antidepressant treatment: assessment of potential risk factors, including CYP2D6 and CYP2C19 polymorphisms, and treatment with CYP2D6 inhibitors.

All adverse drug reaction reports labelled seizures or myoclonus during treatment with antidepressants and stored in the Swedish national database for spontaneous reporting of adverse drug reactions were reviewed in order to evaluate possible risk factors. The reporting physicians were contacted and asked for complementary information, and blood samples for determination of the CYP2D6 and CYP2C19 genotypes were obtained from patients available. In total, 25 cases of seizures and 7 cases of myoclonus were studied. The drugs included were maprotiline (n=8), mianserin (n=7), fluvoxamine (n=6), amitriptyline (n=3), clomipramine (n=3), citalopram (n=2), paroxetine (n=2) and lofepramine (n=1). Previously suggested predisposing factors were identified in all but four cases (87%). None of the 11 patients genotyped were found to be poor metabolizers with respect to the enzymes CYP2D6 or CYP2C19. Thus, neither the CYP2D6 nor the CYP2C19 genotype were found to be associated with the occurrence of seizures/myoclonus during treatment with antidepressants. However, 15 patients (47%) were concomitantly treated with drugs with potential inhibitory effects on CYP2D6, such as neuroleptics and dextropropoxyphene, and the patients might thus have been converted from the extensive metabolizer to the poor metabolizer phenotype during this treatment. Concomitant treatment with drugs decreasing the seizure threshold and/or inhibiting the metabolism of antidepressants appeared to be an important risk factor for the occurrence of seizures/myoclonus.

Adult↗
PubMed1995

Effect of cigarette smoking on fluvoxamine pharmacokinetics in humans.

OBJECTIVES: Although fluvoxamine inhibits the biotransformation of drugs known to be metabolized by CYP1A2, there are no data available with regard to the importance of CYP1A2 for the metabolism of fluvoxamine itself. Because smoking induces the metabolism of drugs catalyzed by CYP1A2, this study investigated the pharmacokinetics of fluvoxamine in smokers and nonsmokers. METHODS: The serum concentration of fluvoxamine was determined by high-performance liquid chromatography for 48 hours after oral administration of a single dose of 50 mg fluvoxamine to 12 smokers (> or = 10 cigarettes per day) and 12 nonsmokers. RESULTS: The smokers had significantly lower areas under the serum concentration-time curve and significantly lower maximal serum concentrations than the nonsmokers (mean +/- SD, 771 +/- 346 versus 1110 +/- 511 nmol.hr.L-1 [p = 0.012] and 39.1 +/- 17.3 versus 57.7 +/- 21.5 nmol.L-1 [p = 0.012], respectively). The terminal elimination half-life did not differ significantly between smokers and nonsmokers (10.1 +/- 1.9 and 10.7 +/- 2.3 hours, respectively). The oral clearance was high among both smokers (4.1 +/- 1.9 L.min-1) and nonsmokers (3.3 +/- 2.7 L.min-1; difference not significant). CONCLUSION: Smokers had lower serum concentrations of fluvoxamine than nonsmokers after a single oral dose of fluvoxamine. This finding is consistent with a possible role of CYP1A2 in fluvoxamine metabolism.

Adult↗