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At least 253 records · Page 14Linked to original sources
PubMed1979

Pirenzepine in the treatment of benign gastroduodenal diseases. A double-blind controlled clinical trial.

Pirenzepine (PRZ, 75 mg/day for 10 days followed by 50 mg/day for 20 days) was compared with placebo (PL) in the treatment of endoscopically confirmed active gastroduodenitis or duodenal ulcer and with carbenoxolone (CB, 300 mg/day followed by 200 mg/day) in the treatment of gastric ulcer in a 30-day double-blind clinical trial. Ninety-seven of 112 outpatients completed the trial. The results can be summarized as follows: a) Gastroduodenitis. Complete normalization of the endoscopic picture was observed in 61% of the 28 patients on PRZ and in 30% of the 27 on PL. b) Duodenal ulcer. Complete endoscopic healing was observed in 75% of the 12 patients on PRZ and in 44% of the 9 on PL. In both studied PRZ induced improvement in clinical symptoms in more patients than PL. c) Gastric ulcer. PRZ and CB induced complete healing in a similar percentage of patients (64% of 11 and 70% of 10 patients). Better results in dyspepsia were observed in the PRZ group than the CB group. No major side-effects and no pathological changes in blood and urine analyses were observed in PRZ-treated patients.

Adolescent↗
PubMed1998

A multicenter, randomized, double-blind trial of 5 versus 10 days of antibiotic therapy for acute otitis media in young children.

BACKGROUND: All but 2 of the 15 published trials have failed to show a difference in efficacy between short (3 to 5 days) and standard (7 to 10 days) antibiotic regimens for acute otitis media (AOM). These studies involved relatively few patients under 2 years of age, who are at a higher risk for treatment failure. METHODS: In a prospective, comparative, double-blind, randomized, multicenter trial, we compared amoxicillin/clavulanate in 3 divided doses for 10 days with an identical 5-day regimen, followed by a 5-day placebo period. RESULTS: Between February 1995 and May 1996, 385 children (mean age, 13.3 months) were enrolled, 194 in the 5-day treatment group and 191 in the 10-day treatment group. In the per protocol analysis, clinical success was obtained on days 12 to 14 after the beginning of treatment (main analysis) in 125 (76.7%) of the 163 children receiving the 5-day regimen and 148 (88.1%) of the 168 receiving the 10-day regimen (P = .006). Clinical success persisted on days 28 to 42 among 57 (40.4%) of the 141 assessable patients in the 5-day group and 64 (46%) of the 139 assessable patients in the 10-day group. (P = .34). Multivariate analysis showed that the 10-day course was statistically superior only among children cared for outside their homes (86.8% vs 70.8%; P = .008). CONCLUSIONS: When assessed on days 12 to 14 after the outset of treatment, a 5-day regimen is not equivalent to a 10-day regimen among young children with AOM.

Acute Disease↗
PubMed2002

Blood pressure response in 24 hours in patients with high blood pressure treated with two nifedipine formulations once a day.

A double-blind, comparative and prospective study with nifedipine once a day was undertaken, in patients with mild and moderate high blood pressure. Blood pressure was measured by mercury sphygmomanometer in two positions: resting and sitting at 3, 6 and 12 weeks of treatment and by ambulatory blood pressure monitoring (ABPM) over 24 h; both were carried out before and after the treatment and the uniformity in the pressure levels were obtained by means of the Smoothness Index. Fifty-four patients were included in the trial, 28 in the microgranules group and 26 in the osmotic pump group. These groups were similar at the baseline in age, gender, weight, height, diastolic and systolic blood pressure. The nifedipine microgranules group had a heart rate higher than the nifedipine osmotic pump group at baseline (X(M) = 75.58 vs. X(B) = 70.75). Blood pressure decreased significantly during the first 3 weeks; 85% in the microgranules group and 75% in the osmotic pump group reached a blood pressure < or =140/90 mm Hg at the end of the study. Three patients in the microgranules group and two in the osmotic pump group required an additional antihypertensive drug. In both groups, the average blood pressure over 24 h was lowered without differences between groups. A decrease was induced in the heart rate in both groups which reached a marginal statistical significance in the microgranules nifedipine group. No changes were induced in the laboratory tests; two patients in the microgranules (8%) nifedipine group and five in the nifedipine osmotic pump group, adverse effects were observed, of which only one in each group required stopping the treatment.

Adult↗
PubMed2003

A retrospective review of sirolimus (Rapamune) therapy in orthotopic liver transplant recipients diagnosed with chronic rejection.

Treatment options are limited for orthotopic liver transplant (OLT) recipients suffering from chronic rejection (CR). We performed a retrospective review of OLT recipients diagnosed with CR and treated with sirolimus. The medical records of all OLT recipients treated with sirolimus between October, 1998 and October, 2000 were retrospectively reviewed. The diagnosis of CR was made by both clinical and histologic criteria: bile duct to hepatic artery ratio less than 0.7, histologic activity index, hepatic arterial wall thickening, and chronic elevation of liver chemistries. Two groups were defined in regard to sirolimus response: sirolimus responders (SR) and sirolimus nonresponders (SNR). Response to treatment was granted only when patients were found to have resolution of abnormal liver transaminases and an improvement in hepatic artery to bile duct ratio. Serum collections for liver chemistries were collected on days 1, 30, 60, and 90. Liver biopsies were reviewed in blinded fashion from day 1 and at least 180 days on therapy by double-blinded pathologists. Sirolimus-related complications were recorded and include drug toxicity, anemia with and without treatment, hospitalizations, infections, immunosuppression complications, lipid profile disorders, edema, muscle aches, and gastrointestinal complaints. Twenty-one patients were diagnosed with CR. The SR group included 13 of 21, and 8 of 21 were in the SNR group. Anemia was diagnosed in 12 of 21 patients: SR, 7 of 13; SNR, 5 of 8; with 5 patients requiring red blood cell transfusions (2 SR, 3 SNR). Recombinant erythropoietin was started in 5 of 21 patients. Sirolimus serum levels were found to be greater than 20 ng/dL in 12 patients. Sirolimus was discontinued in 9 patients,

Adolescent↗
PubMed1993

Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women.

S-adenosyl-L-methionine (SAMe) is a naturally occurring substance which is a major source of methyl groups in the brain and has been found in previous studies to be an effective antidepressant. The aim of this study was to assess the efficacy of oral SAMe in the treatment of depressed postmenopausal women in a 30-day double-blind placebo-controlled randomized trial. During the course of the study, 80 women, between the ages of 45 and 59, who were diagnosed as having DSM-III-R major depressive disorder or dysthymia between 6 and 36 months following either natural menopause or hysterectomy, underwent 1 week of single-blind placebo washout, followed by 30 days of double-blind treatment with either SAMe 1,600 mg/day or placebo. There was a significantly greater improvement in depressive symptoms in the group treated with SAMe compared to the placebo group from day 10 of the study. Side effects were mild and transient.

Climacteric↗
PubMed1997

Controlled-release oxycodone and morphine in cancer related pain.

Controlled-release (CR) formulations of oxycodone and morphine were compared in 45 patients with chronic cancer pain. The study was started with an open-label, randomised titration phase to achieve stable pain control for at least 48 h, followed by a double-blind, randomised, crossover phase in two periods, 3-6 days each. To blind the study using available tablet strengths, the dose ratio of oxycodone to morphine was set at 2:3. A daily telephone contact was maintained between the patient and the investigator. The patients were asked to assess pain intensity four times a day and acceptability of therapy twice daily, and to record possible adverse effects. Pharmacodynamic evaluations were performed at the end of each double-blind period. The patients were allowed to use escape analgesic (respective opioid as oral solution) as needed. Twenty-seven patients were evaluable for both safety and efficacy. Pain was well-controlled during both stable phases. When the period effect was taken into account the two opioids provided comparable analgesia. If the results of the two periods were combined, the patients consumed significantly more escape doses and the mean pain intensities were significantly greater with CR oxycodone. The total opioid consumption ratio of oxycodone to morphine was 2:3 when oxycodone was administered first, and 3:4 when oxycodone was administered after morphine. The total incidence of adverse experiences reported by the patients was similar, but significantly more vomiting occurred with morphine, whereas constipation was more common with oxycodone.

Adult↗
PubMed1984

Duration of incubation of aerobic blood cultures--a comparison of recovery rates following blind subcultures after 0-2, 4 and 9 days.

5,465 aerobic blood culture bottles were examined with 3 blind subcultures: 1. at the arrival of the cultures in the laboratory (0-2 days after their collection), 2. after 4 days' incubation, and 3. after 9 days' incubation. Growth was detected at subculture 1 in 77.0%, at subculture 2 in 20.6% and at subculture 3 in 2.4% of the positive cultures. Only 2 isolates (Staphylococcus aureus 1 bottle, Klebsiella species 1 bottle, 0.48% of total positives) were recovered in the final subculture only.

Aerobiosis↗
PubMed1978

Corticosteroid therapy of alcoholic hepatitis.

Fifty-five patients with alcoholic hepatitis were studied in a 28- to 32-day randomized double blind treatment trial comparing prednisolone (40 mg per day) with placebo therapy. Of 31 placebo-treated patients, 4 died during the study interval and 2 more died within 5 days of study completion. Only 1 of 24 prednisolone-treated patients died during the same interval (Fisher exact test; P = 0.10). Stepwise discriminant analysis of laboratory factors associated with death revealed independently significant associations with prolongation of prothrombin time and height of serum bilirubin at the initiation of the study. When treatment was included as a variable in this discriminant analysis, it was found that corticosteroid therapy significantly decreased mortality (P less than 0.05). The corrected wedged hepatic venous presure decreased to a similar extent in the two groups. These studies suggest that corticosteroid therapy does decrease early mortality in patients with severe alcoholic hepatitis, but has no short term effect on the development of portal hypertension.

Adult↗
PubMed2002

The effects of miglitol on glucagon-like peptide-1 secretion and appetite sensations in obese type 2 diabetics.

BACKGROUND: Previous studies reported that administration of first generation alpha-glucosidase inhibitors (AGIs), such as voglibose or acarbose, produced exaggerated and sustained postprandial responses of glucagon-like peptide-1 (GLP-1), an incretin hormone from the enteroinsular axis, in healthy humans. Little is known about the postprandial release of GLP-1 after AGI therapy in diabetics. GLP-1 plays a role to mediate satiety. Any agent that substantially elevates GLP-1 levels may theoretically reduce hunger, increase satiation and limit food intake. OBJECTIVES: This study was performed to analyse the effect of miglitol, a more potent second generation AGI with fewer gastrointestinal side-effects, on the regulation of meal-related GLP-1 secretion and on the change of insulin-glucose dynamics as well as the release of gastric inhibitory polypeptide (GIP), another incretin hormone, after stimulation by an ordinary meal in obese type-2-diabetic subjects. Miglitol's subsequent influences on appetite sensations and food intake were also measured. DESIGN: In total, 8 obese type-2-diabetic women were randomized to receive treatment with 100 mg of miglitol or placebo three times a day for 2 days (six doses total) in a double-blind fashion. On day 3 of each treatment period (miglitol or placebo), measurements of GLP-1, GIP, insulin and glucose were taken periodically during 3 h after eating a 720 kcal breakfast. Appetite ratings with visual analogue scales (VASs) were used to assess ingestive behaviour hourly just before breakfast and hourly after for 6 h until immediately before lunch. The number of tuna sandwiches eaten at lunch was used to measure food consumption. RESULTS: The plasma GLP-1, glucose, insulin and GIP levels in response to the mixed meal were compared after the miglitol and placebo treatment. Miglitol effectively enhanced postprandial GLP-1 release and suppressed plasma GIP secretion. The ingestion of a mixed meal induced a remarkable rise in GLP-1 after miglitol as compared with placebo in overweight diabetic subjects. The meal-related rise in GLP-1 after miglitol was significantly greater at all time-points between 30 and 180 min than after the placebo. The postprandial incremental area under the curve for GLP-1 with miglitol treatment was about twofold that with the placebo. The GLP-1 level reached a maximum at 120 min after the mixed meal and steadily rose throughout the rest of the 3-h study period. In the miglitol-treated condition, the average caloric intake at lunch during a 30-min eating period was 12% lower (p < 0.05) as compared with that after the placebo in six out of the eight subjects who exhibited a GLP-1 rise after the breakfast meal by greater than 30% from the placebo-treated condition. Correspondingly, the average rating scores were significantly lower for hunger feelings and markedly greater for sensations of satiety under the miglitol treatment; beginning 2 and 3 h, respectively, before the lunch test. CONCLUSIONS: Miglitol induced an enhanced and prolonged GLP-1 release at high physiological concentrations after ingesting an ordinary meal in glycaemic-controlled diabetics. The excessive postprandial GLP-1 elevation after miglitol therapy modified feeding behaviour and food intake, and thereby has potential value in regulating appetite and stabilizing body weight in obese type-2-diabetic patients.

1-Deoxynojirimycin↗
PubMed1999

Suppression of coronary vasculitis in a murine model of Kawasaki disease using an angiogenesis inhibitor.

Coronary arteritis can be induced in C57BL/6 mice with a single intraperitoneal (ip) injection of Lactobacillus casei cell fragments. Histologic sections resemble the vasculitis and aneurysms observed in the medium-sized coronary arteries of children with Kawasaki disease. Since endothelial cells could play an important role in the development of vasculitis, a recently described angiogenesis inhibitor that is not an immunosuppressive agent, AGM-1470 (derived from Aspergillus fumigatus), was used to evaluate its therapeutic potential in this model. A total of 32 mice were administered 0.5 mg of sterile L. casei preparation ip on day 0 and randomized to either a treatment (AGM-1470, 27mg/kg sc alternate days) or a control (vehicle only) protocol. Hearts were harvested on day 14 (early disease) or at the end of the study on day 28 (established disease). Histologic sections were scored blindly for vasculitis. Day 14 sections from both protocols manifested only minimal disease, indicating that the vasculitis had not yet matured. By day 28, the AGM-1470 group had significantly less coronary vasculitis than the control group (0.7 vs 2.6, p < 0.005, respectively). These studies suggest that endothelial cells may play an active role in this pathologic process and that angiogenesis inhibitors, such as AGM-1470, could be useful tools for the treatment and understanding of vasculitis.

Animals↗
PubMed2006

Tryptophan supplementation induces a positive bias in the processing of emotional material in healthy female volunteers.

RATIONALE: The serotonin precursor L-tryptophan (TRP) is available as a nutritional supplement and is licensed as an antidepressant in a number of countries. However, evidence of its efficacy as the primary treatment for depression is limited, and the direct action of TRP on the symptoms of depression and anxiety has not been well-characterised. OBJECTIVES: The present study assessed whether TRP induces cognitive changes opposite to the negative biases found in depression and characteristic of those induced by serotonergic antidepressants in healthy volunteers. MATERIALS AND METHODS: Thirty eight healthy volunteers were randomised to receive 14 days double-blind intervention with TRP (1 g 3x a day) or placebo. On the final day, emotional processing was assessed using four tasks: facial expression recognition, emotion-potentiated startle, attentional probe and emotional categorisation and memory. RESULTS: TRP increased the recognition of happy facial expressions and decreased the recognition of disgusted facial expressions in female, but not male, volunteers. TRP also reduced attentional vigilance towards negative words and decreased baseline startle responsivity in the females. CONCLUSIONS: These findings provide evidence that TRP supplementation in women induces a positive bias in the processing of emotional material that is reminiscent of the actions of serotonergic antidepressants. This highlights a key role for serotonin in emotional processing and lends support to the use of TRP as a nutritional supplement in people with mild depression or for prevention in those at risk. Future studies are needed to clarify the effect of tryptophan on these measures in men.

Adolescent↗
PubMed1994

[Effects of captopril on the cerebral blood flow in the hypertensive aged subjects].

Cerebral blood flow (CBF) was measured in 13 subjects (4 men and 9 women, mean age +/- SD = 63 +/- 7) with moderate, uncomplicated and untreated hypertension and 11 normotensive subjects (6 men and 5 women, mean age +/- SD = 66 +/- 5). A second CBF measurement was performed in hypertensive subjects after a 60 days randomized double blind treatment with either captopril, 75 mg a day (n = 8) or placebo (n = 5). CBF was quantified using the 133Xe inhalation technic and 16 stationary detectors by hemisphere. Comparison of CBF values between hypertensive subjects before treatment and normotensive subjects demonstrated a decrease of CBF in the hypertensive group (49 +/- 9 vs 72 +/- 14 ml/100 g/min; p < 0.001). After the trial the results in the captopril group showed a significant fall in systolic (p < 0.001) and diastolic (p < 0.05) blood pressure and a significant increase in CBF (60 +/- 14 vs 49 +/- 11 ml/100 g/min; p < 0.05). In the placebo group there was no change in blood pressure and CBF (Table). [Table; see text] Our results demonstrate a decrease in CBF of uncomplicated and untreated elderly hypertensive subjects. This decrease is reversible under chronic treatment with captopril.

Aged↗
PubMed1988

Temazepam and recovery in day surgery.

A double-blind trial of temazepam premedication for day cases was undertaken. Effective anxiolysis was recorded in the groups that received temazepam 10 or 20 mg and there was no prolongation of delayed recovery times as measured by memory test cards. All patients were discharged from the day unit 3 hours after the administration of general anaesthesia.

Abortion, Induced↗
PubMed1998

Alternate-day buprenorphine dosing is preferred to daily dosing by opioid-dependent humans.

Alternate-day buprenorphine dosing was compared to daily dosing in opioid-dependent outpatients and choice of alternate-day versus daily dosing was assessed. Four dosing schedules were presented in random order under blind and open dosing conditions. Subjects received two exposures to each dosing schedule. During daily dosing, subjects received maintenance doses every 24 h. During blind alternate-day dosing, subjects received double maintenance doses every 48 h; placebo was interposed on intervening days. During open alternate-day dosing, subjects received twice their maintenance dose on Monday, Wednesday and Friday and maintenance doses on Sunday. After completing two exposures to each dosing schedule, subjects chose either daily or alternate-day schedules each week for 1 month. Study participation was contingent on daily attendance and opioid abstinence. Ten subjects were exposed to the four conditions once. Seven subjects repeated these conditions and participated in the choice phase. The effects of daily versus alternate-day dosing were not influenced by blind or open dosing conditions. Subjects' ratings of withdrawal, "sick" and sedation were lower during daily than during alternate-day dosing, but the difference between treatments was small. Nonetheless, subjects still chose alternate-day dosing on 96% of occasions, suggesting that the subject-rated differences between dosing schedules were not influential. These results extend prior findings to open-dosing conditions, and replicate the safety and acceptability of alternate-day buprenorphine treatment. Choice of alternate-day buprenorphine administration underscores the procedure's clinical utility and potential use as a positive reinforcer to enhance opioid treatment.

Adult↗
PubMed1990

Induction agents for day-case anaesthesia. A double-blind comparison of propofol and midazolam antagonised by flumazenil.

Early postoperative recovery was studied using sedation scoring, measurement of flicker fusion frequency and completion of Trieger test figures in 60 male patients who presented for vasectomy under general anaesthesia as day patients. Anaesthesia was induced in groups 1 and 2 (20 patients each) with mean (SD) doses of 0.16 (0.04) mg/kg or 0.16 (0.03) mg/kg midazolam respectively; group 2 received flumazenil 0.55 (0.19) mg after completion of surgery. The remaining 20 patients (group 3) received propofol 1.50 (0.24) mg/kg. Anaesthesia was maintained with isoflurane vaporized in 33% oxygen and nitrous oxide in all patients. Flumazenil tended to improve tests of recovery after midazolam anaesthesia, but early recovery after propofol anaesthesia was associated with better psychomotor test results and less impairment of mental state as judged by sedation and amnesia scoring.

Adult↗
PubMed2006

Once-daily ofloxacin otic solution versus neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension four times a day: a multicenter, randomized, evaluator-blinded trial to compare the efficacy, safety, and pain relief in pediatric patients with otitis externa.

INTRODUCTION: Otitis externa (OE) is an infection of the external auditory canal affecting children and adults and is associated with symptoms of local pain and tenderness. Twice-daily topical treatment with ofloxacin otic solution (0.3% [Floxin otic solution]) for 10 days has been reported to be as effective and well tolerated as neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension (Cortisporin otic suspension) administered four times daily for 10 days. OBJECTIVE: This study compared the efficacy, safety, and ear-pain resolution of once-daily ofloxacin otic solution (0.3%) versus neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension administered four times daily, in children with OE. RESEARCH DESIGN, PATIENTS, AND METHODS: This multicenter, randomized, parallel-group, evaluator-blinded study was conducted at 34 centers in 278 pediatric OE patients aged 6 months to 12 years. Patients received five drops of ofloxacin otic solution (0.3%) in the affected ears once daily or three drops of neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension four times daily, for 7-10 days. Patient evaluations were performed at pretherapy (day 1), end of therapy (days 7-9), and test of cure (7-10 days post-treatment) visits. Data for 208 patients were clinically evaluable and those for 90 patients were microbiologically evaluable. Scores were obtained for patient assessments of pain severity. MAIN OUTCOME MEASURES: The overall clinical response was cure in the clinically evaluable patients, demonstrated by resolution of OE signs and symptoms at the test of cure visit. The overall clinical-microbiological response was cure in the microbiologically evaluable patients demonstrated by both clinical cure and microbiological eradication. RESULTS: For the clinically evaluable patients, equivalent cure rates were obtained between the once-daily ofloxacin-treated and four-times-daily neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients (93.8% and 94.7%, respectively). For the clinically and microbiologically evaluable patients, the overall cure rates were 96.4% versus 97.1% for the ofloxacin-treated and neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients, respectively. The eradication rates for the prevalent pathogen, Pseudomonas aeruginosa, were 98% versus 100% for ofloxacin-treated and neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients, respectively. Decreases in pain severity were similar in both treatment groups. Statistical analyses were limited by the small numbers of patients in each treatment group. CONCLUSION: In the treatment of OE in children, once-daily ofloxacin otic solution was as effective and safe as neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension given four times daily. The two treatments provide rapid and comparable pain relief; however, ofloxacin otic solution does not have the risk of ototoxicity associated with neomycin and provides effective pain relief without adjunctive steroids.

Administration, Topical↗
PubMed1990

Fosfomycin trometamol in a single dose versus norfloxacin for seven days in the treatment of uncomplicated urinary infections in general practice.

The efficacy and tolerability of fosfomycin trometamol in a single dose of 3 g was compared with norfloxacin 400 mg b.i.d. for seven days in the treatment of adult female patients with uncomplicated urinary infections. 158 female patients with a mean age of 30 years who presented symptoms of dysuria and frequency with documented pyuria and bacteriuria on urinalysis (greater than or equal to 10(5) cfu/ml of urine) were initially included in the study. The total number of clinically and bacteriologically evaluable patients was 111, of which 61 received fosfomycin trometamol and 50 norfloxacin. One to two days after the double blind medication schedule for seven days, 55 of 60 patients (92%) in the fosfomycin trometamol group and 48 of 50 patients (96%) in the norfloxacin group were clinically cured. 37 patients without significant bacteriuria showed a clinical cure rate of over 90% in both therapy groups. Two to three days after the single dose treatment with fosfomycin trometamol the initial infecting pathogen was eradicated in 60 of the 61 patients (98%). One to two days after a seven day treatment with norfloxacin 48 of 50 patients (96%) showed an eradication of the initial infecting pathogen. Six weeks after the start of therapy 39/60 patients (65%) and 32/49 (65%) in the fosfomycin trometamol and norfloxacin groups respectively, remained free from urinary infection. The reinfection rate in both treatment groups was approximately 25%. The relapse rate in the post treatment evaluation period of four weeks was relatively low in both therapy groups, 5/49 patients (10%) in the norfloxacin group and 3/55 patients (6%) in the fosfomycin trometamol group, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2001

Different effects of St John's wort on the pharmacokinetics of simvastatin and pravastatin.

OBJECTIVE: St John's Wort, a widely used herbal product, is an inducer of CYP3A4 and it decreases blood concentrations of CYP3A4 substrates. The effects of St John's Wort on the pharmacokinetics of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors simvastatin (an inactive lactone pro-drug) and pravastatin were determined in this study. METHODS: Sixteen healthy male subjects (n = 8 in group 1 and n = 8 in group 2) took a St John's Wort caplet (300 mg) or matching placebo three times a day for 14 days in a double-blind, crossover study. On day 14, a single oral dose of 10 mg simvastatin and 20 mg pravastatin was given to subjects in group 1 and group 2, respectively. Blood samples were obtained during a 24-hour period after the administration of each drug. RESULTS: Repeated St John's Wort treatment tended to lower plasma simvastatin concentration and significantly (P <.05) lowered concentrations of simvastatin hydroxy acid, its active metabolite. The peak concentration in plasma (ratio, 0.72 of placebo) of simvastatin hydroxy acid tended to be decreased and its area under the plasma concentration-time curve between time zero and 24 hours after administration (ratio, 0.48 of placebo) was significantly decreased (P <.05) by St John's Wort. On the other hand, St John's Wort did not influence plasma pravastatin concentration. No significant differences were observed in the elimination half-life of simvastatin or pravastatin between the placebo and St John's Wort trials. CONCLUSIONS: This study showed that St John's Wort decreases plasma concentrations of simvastatin but not of pravastatin. Because simvastatin is extensively metabolized by CYP3A4 in the intestinal wall and liver, which are induced by St John's Wort, it is likely that this interaction is partly caused by the enhancement of the CYP3A4-mediated first-pass metabolism of simvastatin in the small intestine and liver.

Adult↗