ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb03943.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Migraine is a common and debilitating disorder of uncertain pathogenesis. Recent research into the pathophysiology of migraine and serotonin receptors has revolutionized the approach to pharmacotherapy. New medications, such as sumatriptan, and new dosage forms of older medications, including dihydroergotamine, NSAIDs, and phenothiazines are available to treat acute attacks. New prophylactic approaches include the use of calcium‐channel blockers, NSAIDs, fluoxetine, and valproate. The addition of several new agents for the acute and prophylactic therapy of migraine has improved the outlook for this disabling disorde

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb03944.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Unlabeled use of drugs in children occurs frequently and contributes to the therapeutic orphan dilemma. This situation can no longer be condoned; few acceptable reasons still exist for not evaluating potentially effective drug therapy in children. An apparent lack of research funds is not one of these reasons; only allocation of these funds to pediatric pharmacology is found wanting. Availability of clinical pharmacology programs, pediatric pharmacology manpower, sensitive analytical techniques, and acceptable ethical approaches to pediatric research reveal that drug evaluation is feasible in children. Studies readily include the required therapeutic indication for drug use in pediatrics. Efforts of academia, government and industry are now converging to show that the path for the noble mission of pediatric pharmacology—rational use of FDA approved drugs for children—is now clear for act

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb03945.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Breastfeeding is an essential physiologic process that provides nutrition to the infant and protects the child against infection and immunologic disorders. The incidence of various diseases and metabolic disorders is known to be less in a breastfed infant compared with a child given a milk substitute. Psychologically, a breastfed infant forms a maternal bond that enables adaptation more readily to a social environment. It is well‐established that all drugs are excreted into breast milk and are bioavailable to the infant. In general the majority of drugs do not pose a significant problem to the nursing in/ant and breastfeeding should be encouraged. The physician should be aware of which drugs are contraindicated during lactation and which drugs should be used with caution. There are also environmental chemicals that readily enter breast milk and may induce adverse effects. At present, the advantages of breastfeeding for infant development outweigh the potential adverse consequences and this physiologic process should be encouraged. With the use of available data on pharmacokinetics, milk‐to‐plasma ratio, excretion, etc. a supportive approach can be delineated by the pediatrician to reassure the nursing mother that they can safely breastfeed and continue therapy with minimal effects on the infant. It is thus imperative to document the extent to which a drug or chemical appears in breast milk and any apparent effects in the i

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb03946.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The effect of durations of diltiazem pretreatment on nifedipine kinetics was evaluated. Eighteen healthy male subjects were randomly allocated to three groups, 6 subjects each, for single doses of 60 mg diltiazem, and 3 days and 6 days with diltiazem 60 mg three times a day. All subjects received 20 mg nifedipine orally on two occasions using a double‐blind cross‐over, placebo‐controlled method. No significant difference on pharmacokinetic parameters of nifedipine without diltiazem were observed among three groups. The single dose with 60 mg diltiazem significantly increased the area under the plasma concentration‐time curve (AUC) for nifedipine compared with that in control an average of 35.1% (P<.05) and decreased the total body clearance (CL) an average of 24.0% (P<.05). Three days and 6 days pretreatment with diltiazem 60 mg three times a day significantly increased mean nifedipine AUC to 151.1% (P<.01), 188.0% (P<.05) of control values, and decreased CL to 58.2% (P<.01), 63.9% (P<.05) of control values, respectively. The elimination half‐life (t1/2) of nifedipine were significantly prolonged both after 3 days' and after 6 days' pretreatment of diltiazem. These results suggest that diltiazem affects the nifedipine kinetics rapidly and pretreatment duration dependently. A clinically important drug interaction may occur when both drugs are administered simul

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb03947.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Inhibitors of HMG‐CoA reductase are new safe and effective cholesterol‐lowering agents. Elevation of alanine‐amino transferase (ALT) and aspartate‐amino transferase (AST) has been described in a few cases and a myopathy with elevation of creatinine kinase (CK) has been reported rarely. The inhibition of HMG‐CoA reductase affects also the biosynthesis of ubiquinone (CoQ10). We studied two groups of five healthy volunteers treated with 20 mg/day of pravastatin (Squibb, Italy) or simvastatin (MSD) for a month. Then we treated 30 hypercholesterolemic patients in a double‐blind controlled study with pravastatin, simvastatin (20 mg/day), or placebo for 3 months. At the beginning, and 3 months thereafter we measured plasma total cholesterol, CoQ10, ALT, AST, CK, and other parameters (urea, creatinine, uric acid, total bilirubin, gamma GT, total protein). Significant changes in the healthy volunteer group were detected for total cholesterol and CoQ10 levels, which underwent about a 40% reduction after the treatment. The same extent of reduction, compared with placebo was measured in hypercholesterolemic patients treated with pravastatin or simvastatin. Our data show that the treatment with HMG‐CoA reductase inhibitors lowers both total cholesterol and CoQ10 plasma levels in normal volunteers and in hypercholesterolemic patients. CoQ10 is essential for the production of energy and also has antioxidative properties. A diminution of CoQ10 availability may be the cause of membrane alteration with consequent ce

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb03948.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The pharmacokinetics, safety, and pharmacologic effects of OPC‐21268, a nonpeptide orally active vasopressin V1 receptor antagonist, have been investigated in 33 healthy subjects. First, 24 subjects were randomly divided into 3 groups of 8, 6 of whom were given 2 ascending single oral doses out of 6 (10, 50, 150, 300, 450, and 600 mg) of OPC‐21268 after an overnight fast. The remaining two subjects in each group received placebo as control at each dosing. Additionally, after this procedure, the 6 subjects who received 50‐mg single doses were given the same dose in a nonfasting condition. After the single‐dose study was completed and the safety and tolerability were ascertained, the remaining 9 subjects, including 3 controls, were given 300 mg of the drug 3 times daily for 7 days (days 3–9) and were given single 100‐mg oral doses before (day 1) and after (day 10) this repeated‐dose study. OPC‐21268 plasma concentrations declined in a monoexponential or biexponential pattern after reaching the maximum plasma concentrations (Cmax). The mean (± standard error of the mean) plasma half‐life (t1/2) of the α phase ranged from 1.31 ± 0.11 to 1.78 ± 0.15 hours, and the mean t1/2 of the β phase ranged from 4.31 ± 0.28 to 6.28 ± 0.59 hours. The area under the concentration (AUC0‐∞) and Cmax were proportional to the dose (P<.001). The mean apparent oral clearance ranged from 6.24 ± 0.62 to 10.22 ± 0.79 L/h, and the mean percentage fraction of administered dose excreted unchanged in the urine up to 48 hours ranged from 0.39 ± 0.03 to 1.02 ± 0.09%. The mean tmax (the time taken to reach Cmax) was 1.03 ± 0.23 hours. The nonfasting condition lengthened the mean tmax significantly from 0.5 to 1.75 ± 0.10 hours, but did not alter the other kinetic parameters. The simulation curve for repeated dosing predicted from the plasma concentration‐time relationship after the single dosing on day 1 corresponded well with that obtained from the actual data. There were no significant differences in pharmacokinetic parameters between the first (day 1) and final (day 10) administrations, and the parameters were also compatible with those obtained in the single‐dose study. In the single‐ and repeated‐dose studies, the drug did not alter the blood pressure or the heart rate throughout the study period. Further plasma vasopressin levels were not changed and remained within the normal range throughout the two study periods. No increase in urine volume occurred after single or repeated OPC‐21268 administration. The results suggest that the plasma concentration of OPC‐21268 increases in proportion to the dose. Its elimination is dose independent and is not changed on repeated administration. The drug is not likely to influence hemodynamics, plasma vasopressin, or urine output. Oral doses up to 600 mg for single administration and 100 mg three times daily for repeated dosing for the period of 7 days, are on the basis of the cur

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb03949.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Stress adversely affects glycemic control in patients with type II diabetes mellitus. In addition, stress reduction with relaxation techniques or medication use in the management of hyperglycemia has been recommended. This study examined the relationship of glycemic control to self‐reported stress in 19 patients with type II diabetes mellitus who were randomly allocated to receive either glyburide or glipizide for 16 weeks in a double‐blind crossover design. Each treatment phase was preceded by a 2‐week washout period. A previously designed and validated nine‐item stress questionnaire was used to assess areas such as safety, financial wellbeing, energy level, health, etc. These areas were evaluated as more/less, better/worse, or no change. The stress questionnaire, fasting blood glucose (FBG), and glycosylated hemoglobin (GHb) concentrations were completed or measured at the end of glyburide and glipizide treatment periods. By assigning a value of 1, 2, or 3 to a positive, no change, or negative response, respectively, a composite stress score was computed and compared with glycemic control as assessed by FBG and GHb. Regression analysis showed highly significant correlations (P<.05) between stress scores and FBG (r = .70) as well as GHb (r = 0.84) with glipizide therapy. No such correlation was noted with glyburide (FBG: r = 0.29; GHb: r = 0.29). These findings suggest that during glyburide treatment, in contrast to glipizide, an increase in stress was not associated with a corresponding rise in blood glucose or worsening of metabolic control. In view of the clinical relevance of this glyburide “blunting” effect on stress‐induced hyperglycemia, further investigations measuring circulating catecholamines and cortisol concentrations are required to confirm this ending and to characterize the underly

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb03950.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Stable isotope labeling in therapeutic and subtherapeutic quantities of drug (15N213C‐phenobarbital) can be quantitated in biological matrices (urine) and high performance liquid chromatography (HPLC) peaks from urine using continuous‐flow isotope‐ratio mass spectrometry (CF‐IRMS). Standard curves for15N213C‐phenobarbital were reproducible and linear (R2>0.985) over the ranges of 3–100 μg/mL for whole urine (1SN2or13C labeling) and 0.1–8.0 μg/mL for HPLC peaks derived from urine (15N2labeling). The lower limit of quantitation values for urine drug concentration was 0.46–2.62 μg/mL in whole urine and 0.10–0.70 μg/mL in HPLC peaks. Validation samples quantitated with these standard curves yielded close to expected values. These data suggest stable isotope labeling and CF‐IRMS may be used as an alternative to14C labeling and radioactivity counting methods in mass balance/metabolite identification and o

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb03951.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

To assess prescribing practices for androgens at Wilford Hall USAF Medical Center, the authors analyzed prescriptions for all patients receiving therapy during a 12‐month period (n = 201) and reviewed the available outpatient records not maintained elsewhere (n = 105). The most commonly prescribed androgens were testosterone enanthate (144/201; 56.7%), and danazol (52/201; 25.9%). Review of the available outpatient medical records of 73 male patients using testosterone enanthate showed a mean age of 59.5 years, mean frequency of injection of 20 days, mean duration of therapy of 3.5 years, and mean dose of 226 mg. Therapy was initiated by a urologist (34/73; 46.6%), an endocrinologist (33/73; 45.2%), or an internist (6.73; 8.2%). Indications for therapy based on pretreatment laboratory and historical data included hypergonadotropic hypogonadism (24/73; 32.9%), hypogonadotropic hypogonadism (23/73; 31.5%), unspecified hypogonadism (7/73; 9.6%), and empiric treatment of elderly men with erectile dysfunction without evidence of hypogonadism (9/73; 26%). Pretreatment prostate examinations as well as measurement of serum testosterone (66/73; 90.4%) and serum gonadotropins (52/73; 71.2%) were often not performed. The authors conclude that records of patients treated with androgens show: 1) Doses are appropriate; 2) Empiric treatment of erectile dysfunction in elderly men is common despite the associated risks; 3) Laboratory and physical evaluation before treatment is often incomplete; 4) There was no evidence of androgenic substance abuse in patients studie

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb03952.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY