Abstract：
:Four protease inhibitor antiviral agents (ritonavir, indinavir, nelfinavir, saquinavir) were evaluated as in vitro inhibitors of the activity of six human cytochromes using an in vitro model based on human liver microsomes. Ritonavir was a highly potent inhibitor of P450-3A activity (triazolam hydroxylation), having inhibitory potency slightly less than ketoconazole. Indinavir was also a potent 3A inhibitor, while nelfinavir and saquinavir were less potent. Ritonavir had high inhibition potency against cytochrome P450-2C9 (tolbutamide hydroxylation), -2C19 (S-mephenytoin hydroxylation), and -2D6 (dextromethorphan O-demethylation and desipramine hydroxylation), while the other protease inhibitors had one or more orders of magnitude lower inhibitory activity against these reactions. None of the protease inhibitors had important inhibitory potency against P450-1A2 (phenacetin O-deethylation) or -2E1 (chlorzoxazone hydroxylation). Thus, among available protease inhibitors, ritonavir carries the highest risk of incurring drug interactions due to inhibition of cytochrome P450 activity.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
von Moltke LL,Greenblatt DJ,Grassi JM,Granda BW,Duan SX,Fogelman SM,Daily JP,Harmatz JS,Shader RIdoi
10.1002/j.1552-4604.1998.tb04398.xsubject
Has Abstractpub_date
1998-02-01 00:00:00pages
106-11issue
2eissn
0091-2700issn
1552-4604journal_volume
38pub_type
杂志文章abstract：:The aim of this study was to test the usefulness of the metabolite/caffeine ratio for the evaluation of hepatic dysfunction. Subjects with liver cirrhosis and chronic hepatitis, as well as healthy volunteers, were given the oral dose of 300 mg caffeine. Blood samples were collected after 4, 8, and 12 hours. Concentrat...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270004263468
更新日期：2004-04-01 00:00:00
abstract：:The onset and offset of the electropharmacologic effect of procainamide was studied in nine patients with ventricular arrhythmias. Procainamide was given at a constant infusion rate of 0.27 +/- 0.05 mg/kg/min for 50 to 60 minutes to an average total dose of 15.5 +/- 4.4 mg/kg. The QRS interval (used as an index of ele...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1988.tb03118.x
更新日期：1988-11-01 00:00:00
abstract：:The short-term effect of the blockade of the beta-adrenergic receptors on serum lipoproteins and the plasma activities of the enzymes involved in the metabolism of the serum lipoproteins: lipoprotein lipase (LPL), hepatic lipase (HL) and lecithin: cholesterol acyltransferase (LCAT) was evaluated in ten healthy normoli...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1987.tb03052.x
更新日期：1987-07-01 00:00:00
abstract：:Blood concentrations of cyclosporine were determined in adult and pediatric patients following orthotopic liver transplantation to quantitate cyclosporine blood clearance and oral absorption. Seventeen bioavailability studies were performed following transplantation surgery in nine children and seven adults. The intra...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1986.tb02966.x
更新日期：1986-11-01 00:00:00
abstract：:Sixteen essential hypertensive patients were entered into a protocol assessing the effect of Spirapril, an angiotensin-converting enzyme (ACE) inhibitor, on blood pressure, the renin-aldosterone system, and renal function. Specifically monitored before, during 6 weeks, and 6 months of Spirapril therapy were plasma ren...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1993.tb04668.x
更新日期：1993-04-01 00:00:00
abstract：:Acebutolol, a beta-1 selective beta blocker with intrinsic sympathomimetic activity has been shown to be an effective agent in chronic angina pectoris therapy, with twice or three times daily dosing. The long-term effects of 400 mg of acebutolol given only once a day versus placebo on exercise hemodynamics, ST segment...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1988.tb05754.x
更新日期：1988-05-01 00:00:00
abstract：:The aim of this study was to determine the relationship, precision, and bias of a propofol target-controlled infusion (TCI) system during prolonged infusion in neurosurgical patients. We retrospectively included patients undergoing general anesthesia for elective neurosurgical removal of brain tumors and postoperative...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1060
更新日期：2018-05-01 00:00:00
abstract：:The number of worldwide and Asian multiregional clinical trials (MRCTs) submitted for Japanese New Drug Applications increased markedly between 2009 and 2013, with an increasing number performed for simultaneously submission in the USA, EU, and Japan. Asian studies accounted for 32% of MRCTs (14/44 studies) and had co...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.273
更新日期：2014-07-01 00:00:00
abstract：:A decrease in dietary protein intake lowers the clearance of a number of substances excreted principally by the kidney including uric acid and oxypurinol, the major metabolite of allopurinol. We studied the kinetics of uric acid and oxypurinol in seven healthy volunteers on a normal protein diet (2600 calories; 100 g ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1989.tb03239.x
更新日期：1989-01-01 00:00:00
abstract：:The effect of pomegranate juice (PJ) or grapefruit juice (GFJ) on CYP3A activity was studied in vitro and in healthy human volunteers. In human liver microsomes, the mean 50% inhibitory concentrations (IC(50)) for PJ and GFJ versus CYP3A (triazolam alpha-hydroxylation) were 0.61% and 0.55%, (v/v) respectively, without...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270006298359
更新日期：2007-03-01 00:00:00
abstract：:The antipyretic activity of ibuprofen (Brufen) and paracetamol (Crocin) was compared in 22 children with pyrexia who received either ibuprofen or paracetamol in syrup form. Both axillary and rectal temperatures were recorded prior to drug administration and 1/2, 1, 2, 3, 4, 5, 6, 8, and 12 hours after dosing. Analysis...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1980.tb01685.x
更新日期：1980-11-01 00:00:00
abstract：:ABT-761 is a second-generation 5-lipoxygenase inhibitor in clinical development for the treatment of asthma. The effects of ABT-761 on the pharmacokinetics of an oral contraceptive were assessed in 21 female adult volunteers in a phase I, multiple-dose, open-label study. Subjects received a single dose of oral contrac...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1998.tb04472.x
更新日期：1998-07-01 00:00:00
abstract：:This experiment represents the first time that it has been possible to measure a body fluid compartment by direct means during spaceflight. Based on the results observed in the five crewmen in this study, it is concluded that TBW decreases by 3.4% after 1 to 3 days of exposure to microgravity in the Space Shuttle. Som...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1991.tb03663.x
更新日期：1991-10-01 00:00:00
abstract：:Despite a paucity of data, the role of intravenous lidocaine (IVLI) as adjunctive analgesia in the intensive care unit (ICU) seems promising due to a low potential to contribute to respiratory depression. A retrospective chart review was conducted to evaluate the safety and effectiveness of IVLI for the treatment of p...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1002/jcph.874
更新日期：2017-07-01 00:00:00
abstract：:Compared with aminoglycosides, chloramphenicol, sulfonamides, tetracyclines, and even penicillins, the cephalosporins represent a remarkably safe class of antibiotics. Among the cephalosporins, the extended spectrum, third generation agents developed generally produce few side effects and appear to be less allergenic ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/j.1552-4604.1990.tb03476.x
更新日期：1990-05-01 00:00:00
abstract：:DS-1040, a low-molecular-weight imidazole derivative, inhibits the enzymatic activity of thrombin-activatable fibrinolysis inhibitor (TAFIa), enhancing endogenous tissue plasminogen activator-triggered fibrinolysis. This first-in-human, randomized, placebo-controlled, phase 1 study evaluated the safety, pharmacokineti...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.1474
更新日期：2019-12-01 00:00:00
abstract：:Lemborexant is a novel orexin receptor antagonist approved in the United States and Japan for the treatment of insomnia. This article describes the population pharmacokinetics (PK) of lemborexant and the relationship of its daily steady-state exposure (Cav,ss ) to the probability of most frequent treatment-emergent ad...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1683
更新日期：2020-12-01 00:00:00
abstract：:The authors examined the pharmacokinetics of the CD19 receptor-directed tyrosine kinase inhibitor B43-Genistein in 17 patients (4 children, 13 adults) with B-lineage lymphoid malignancies, including 12 patients with acute lymphoblastic leukemia (ALL) and 5 patients with non-Hodgkin's lymphoma (NHL). The immunoconjugat...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/00912709922012051
更新日期：1999-12-01 00:00:00
abstract：:This study assessed the efficacy and safety of ketoprofen patch compared with placebo in patients who had rheumatoid arthritis and persistent wrist pain. Patients (N = 676)who had achieved systemic disease control with a disease-modifying antirheumatic drug and/or systemic corticosteroid, but still had persistent wris...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270009355813
更新日期：2010-10-01 00:00:00
abstract：:The safety and efficacy of intravenous (i.v.) torsemide as adjunctive therapy for acute cardiogenic pulmonary edema was evaluated. Thirteen patients were treated with i.v. torsemide and six patients, with i.v. furosemide, as a positive control. Doses of torsemide, 20 mg or 40 mg, and furosemide, 40 mg or 80 mg, were a...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1002/j.1552-4604.1994.tb01985.x
更新日期：1994-11-01 00:00:00
abstract：:Because of the key role blood viscosity plays in the regulation of blood pressure (BP) and the hemorheological effects of pentoxifylline (PTX), this study was conducted to evaluate whether PTX can reduce BP when added to captopril in patients with stage 1 hypertension. In this randomized clinical trial 62 patients wit...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1516
更新日期：2020-02-01 00:00:00
abstract：:Although glucocorticoids and cyclosporine are frequently used to treat patients with various types of glomerulopathy, clinical responses to treatment vary considerably. Considerable interindividual heterogeneity in the suppressive effects of glucocorticoids on lymphocyte proliferation in vitro has been previously repo...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1996.tb04760.x
更新日期：1996-10-01 00:00:00
abstract：:The pharmacokinetics (PK) and safety of single-dose buparlisib (30 mg) were assessed in subjects with mild to severe hepatic impairment (n = 6 each) relative to healthy controls (n = 13). Blood samples were collected until 336 hours postdose and evaluated by liquid chromatography tandem mass spectrometry. PK parameter...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.590
更新日期：2016-03-01 00:00:00
abstract：:A randomized, dose-escalating study evaluated the pharmacokinetics of single and multiple oral doses of pirfenidone, a promising antifibrotic agent, in 48 healthy Chinese volunteers. The effects of sex and food on the pharmacokinetics of pirfenidone were also evaluated. Pharmacokinetics was determined from serial bloo...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270007304104
更新日期：2007-10-01 00:00:00
abstract：:Using a sensitive and specific radioimmunoassay the pharmacokinetic disposition of clonidine was determined in hypertensive patients after a single dose and then after 5, 28 and 56 days of chronic dosing with 75 micrograms bd. Following a single dose of clonidine maximal plasma concentrations of 0.34 +/- 0.06 ng/ml we...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1989.tb03335.x
更新日期：1989-04-01 00:00:00
abstract：:Ixekizumab (LY2439821), a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody that selectively binds and neutralizes interleukin (IL) 17A has demonstrated efficacy in the treatment of psoriasis. A population pharmacokinetics-pharmacodynamics model was developed using NONMEM 7.2 to describe the temporal re...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1002/jcph.312
更新日期：2014-10-01 00:00:00
abstract：:Research into the distribution of medication errors usually focuses on isolated stages within the medication use process. Our study aimed to provide a novel process-oriented approach to medication incident analysis focusing on medication error chains. Our study was conducted across a 900-bed teaching hospital in Switz...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.319
更新日期：2014-10-01 00:00:00
abstract：:This open-label, crossover study had two objectives: to compare the steady-state pharmacokinetics of high-dose telmisartan with and without coadministered high-dose hydrochlorothiazide and to compare the steady-state pharmacokinetics of hydrochlorothiazide with and without coadministered telmisartan. A total of 13 hea...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：2000-12-01 00:00:00
abstract：:Microgravity is produced for 20 to 30 seconds in NASA's KC-135 aircraft at the end of a 2 G pullup for each of 40 parabolas per flight. Continuous transcranial Doppler ultrasound, arterial blood pressure, and acceleration levels were recorded for 12 male and 8 female healthy subjects without known cardiovascular or ce...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1991.tb03648.x
更新日期：1991-10-01 00:00:00
abstract：:X-linked hypophosphatemia (XLH) is an inherited metabolic bone disease with abnormally elevated serum FGF23 resulting in low renal maximum threshold for phosphate reabsorption, low serum phosphate (Pi) and 1,25-dihydroxyvitamin D levels with subsequent development of short stature and skeletal deformities. KRN23 is a ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.611
更新日期：2016-04-01 00:00:00
