Abstract:
:Cyclophosphamide-based regimens are front-line treatment for numerous pediatric malignancies; however, current dosing methods result in considerable interpatient variability in tumor response and toxicity. In this pediatric population, the authors' objectives were (1) to quantify and explain the pharmacokinetic variability of cyclophosphamide and 2 of its metabolites, hydroxycyclophosphamide (HCY) and carboxyethylphosphoramide mustard (CEPM), and (2) to apply a population pharmacokinetic model to describe the disposition of cyclophosphamide and these metabolites. A total of 196 blood samples were obtained from 22 children with neuroblastoma receiving intravenous cyclophosphamide (400 mg/m2/d) and topotecan. Blood samples were quantitated for concentrations of cyclophosphamide, HCY, and CEPM using liquid chromatography-mass spectrometry and analyzed using nonlinear mixed-effects modeling with the NONMEM software system. After model building was complete, the area under the concentration-time curve (AUC) was computed using NONMEM. Cyclophosphamide elimination was described by noninducible and inducible routes, with the latter producing HCY. Glomerular filtration rate was a covariate for the fractional elimination of HCY and its conversion to CEPM. Considerable interpatient variability was observed in the AUC of cyclophosphamide, HCY, and CEPM. These results represent a critical first step in developing pharmacokinetic-linked pharmacodynamic studies in children receiving cyclophosphamide to determine the clinical relevance of the pharmacokinetic variability in cyclophosphamide and its metabolites.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
McCune JS,Salinger DH,Vicini P,Oglesby C,Blough DK,Park JRdoi
10.1177/0091270008325928subject
Has Abstractpub_date
2009-01-01 00:00:00pages
88-102issue
1eissn
0091-2700issn
1552-4604pii
0091270008325928journal_volume
49pub_type
杂志文章,多中心研究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::A drug-drug interaction study was conducted to determine whether ritonavir (200 mg; 4 doses over 2 days) alters the pharmacokinetic disposition of bupropion (75 mg; once) coadministered to 7 healthy volunteers in a placebo-controlled 2-way crossover study. Serum samples collected from 0 to 24 hours after bupropion adm...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270006286981
更新日期:2006-05-01 00:00:00
abstract::GS-9667, a new selective, partial agonist of the A(1) adenosine receptor (AR), may represent an effective therapy for Type 2 diabetes (T2DM) and dyslipidemia via lowering of free fatty acids (FFA). The objectives of the studies were to evaluate the effects of single and multiple doses of GS-9667 on plasma FFA concentr...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.9
更新日期:2013-04-01 00:00:00
abstract::The effect of lovastatin given before percutaneous coronary angioplasty (PTCA) on early restenosis was investigated in men with mild to moderate hypercholesterolemia. Thirty-four hypercholesterolemic patients (serum LDL cholesterol 130-200 mg/dL) undergoing their first PTCA completed a 6-month prospective, double-blin...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/j.1552-4604.1995.tb05017.x
更新日期:1995-06-01 00:00:00
abstract::A selective thromboxane (TX) synthase inhibitor, CS-518, was orally administered to healthy male Japanese volunteers and the pharmacokinetic and pharmacodynamic properties were investigated. The time profile of drug concentrations in plasma was determined, and the effects of the drug on platelet aggregation in plasma ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1994.tb03964.x
更新日期:1994-01-01 00:00:00
abstract::The pharmacokinetics, pharmacodynamics, and safety of fosinopril sodium (SQ 28,555), a new orally active angiotensin-converting enzyme (ACE) inhibitor, was evaluated in 73 healthy men in two separate studies. In study I, doses ranging from 10 to 640 mg were administered once daily for 3 days to seven groups of five su...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1991.tb01887.x
更新日期:1991-01-01 00:00:00
abstract::The present study was conducted to determine the absolute bioavailability of fimasartan (FMS; Kanarb(®) ) after the single oral administration of a 60-mg tablet or a single 30-mg intravenous (IV) infusion. This investigation was a randomized, single-dose, open-labeled, two-way crossover study of 16 healthy Korean male...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1002/jcph.618
更新日期:2016-05-01 00:00:00
abstract::Coronary heart disease, hypertension, and dyslipidemia are highly prevalent and commonly coexist in people who are middle-aged and older. Previous data suggested that lowering cholesterol concentrations in individuals at high risk of cardiovascular disease improved clinical outcomes. Xuezhikang, a partial extract of r...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1177/0091270009337509
更新日期:2009-08-01 00:00:00
abstract::The authors evaluated the effect of high-dose aspirin at a therapeutic dose, using chlorzoxazone as a probe for CYP2E1 enzyme activity. In a randomized, open-label, 2-way crossover study, 10 healthy men were treated 3 times daily for 6 days with 1 g aspirin or placebo. On day 7, 1 dose of 400 mg chlorzoxazone was admi...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/0091270005282635
更新日期:2006-01-01 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::The drug-drug and drug-food interactions between tenofovir DF and didanosine EC were evaluated in 2 pharmacokinetic studies in healthy adult subjects. When 400 mg was dosed with tenofovir DF, mean didanosine AUC was increased by 44% to 60% following fasted or fed administration. Staggered coadministration (2 hour, fas...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/0091270005281351
更新日期:2005-12-01 00:00:00
abstract::Several approaches are available to estimate the glomerular filtration rate (GFR) from the sinistrin clearance. To compare such approaches, GFR was estimated in six healthy volunteers, both after a bolus injection and a bolus dose followed by a 6-hour infusion. A recently developed high-performance liquid chromatograp...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1997.tb04355.x
更新日期:1997-08-01 00:00:00
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 i...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1998.tb04398.x
更新日期:1998-02-01 00:00:00
abstract::The angiotensin-converting enzyme (ACE) gene is a candidate genetic locus for coronary artery disease (CAD). Studies investigating the relationship between the ACE-insertion/deletion (I/D) gene polymorphism and myocardial infarction (MI) have been inconsistent. The authors hypothesized that age may be an important mod...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/0091270010382420
更新日期:2011-09-01 00:00:00
abstract::Guidelines have been developed by the Bureau of Drugs, FDA, for antinflammatory drug development. They address the problem of efficacy and safety testing but leave the definition of qualified investigators and appropriate subjects unstated. The natural history of rheumatoid arthritis, the most-studied chronic inflamma...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1977.tb01544.x
更新日期:1977-11-01 00:00:00
abstract::Data from 60 patients treated with amikacin were analyzed for factors associated with nephrotoxicity. In 42 of these patients, data were examined for factors associated with clinical outcome. Variables evaluated included patient weight, age, sex, serum creatinine level, creatinine clearance, duration of therapy, total...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1986.tb02910.x
更新日期:1986-02-01 00:00:00
abstract::In patients with renal insufficiency, dose adjustments based on creatinine clearance and body weight have been a component of imipenem dosage instructions. The objective of the current analysis was to provide revised dosing recommendations by evaluating the impact of creatinine clearance and body weight on the pharmac...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/jcph.1356
更新日期:2019-05-01 00:00:00
abstract::UCN-01 is a protein kinase inhibitor under development as a novel anticancer drug. The initial pharmacologic features in patients were not predicted from preclinical experiments. The distribution volume and the systemic clearance were much lower than those in experimental animals (mice, rats, and dogs), and the elimin...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1177/0091270005274549
更新日期:2005-04-01 00:00:00
abstract::The decrease in renal blood flow (RBF) observed in patients with hypertension can be increased with converting enzyme inhibition (CEI). It is unknown whether the decrease in RBF observed with age can also be increased with CEI. This study compared the short- and long-term effects of captopril monotherapy in young (les...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1991.tb01888.x
更新日期:1991-01-01 00:00:00
abstract::A two-period, crossover trial was conducted in the hypobaric chamber on human subjects to compare the influence of inflight exercise (experimental) and restricted activity (control) on altitude decompression sickness (DCS) during simulated extravehicular activities. Out of 39 pairs (total of 78 exposures), 4 cases of ...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1994.tb02012.x
更新日期:1994-06-01 00:00:00
abstract::The pharmacokinetics of enoximone and its sulfoxide metabolite were determined following administration of a single oral dose of 1 or 2 mg/kg in seven patients with congestive heart failure, and in two normal volunteers following a single 75-mg capsule, and were compared to those published previously. Plasma concentra...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1987.tb03083.x
更新日期:1987-09-01 00:00:00
abstract::Nadolol-14C, 2,3-cis-5-(3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy)-1,2,3,4-tetrahydro-2,3-naphthalenediol, a nonselective beta-adrenergic blocking agent, was administered orally and intravenously at 2-mg doses to patients with mild cases of essential hypertension. Terminal plasma half-times after oral and intraven...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1977.tb04609.x
更新日期:1977-05-01 00:00:00
abstract::The incidence of migraine is higher among women than men and peaks during the reproductive years, when contraceptive medication use is common. Atogepant, a potent, selective antagonist of the calcitonin gene-related peptide receptor-in development for migraine prevention-is thus likely to be used by women taking oral ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1610
更新日期:2020-09-01 00:00:00
abstract::In 14 patients with congestive heart failure (CHF) of various grade (NYHA class 2-4) the effects of zofenopril calcium (SQ 26,991) on blood pressure and forearm circulation were studied by venous occlusion plethysmography. Changes in plasma renin activity (PRA), aldosterone, Atrial natriuretic factor (ANF) and arginin...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1989.tb03282.x
更新日期:1989-12-01 00:00:00
abstract::The impact of a microgravity simulation using a head-down tilt (-6 degrees) on lidocaine pharmacokinetics used as a probe to evaluate hepatic blood flow is discussed. Eight healthy male subjects were selected for a 7-day study, including a 4-day head-down tilt from day 2 to day 5. Subjects were given 1 mg/kg of lidoca...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1995.tb04110.x
更新日期:1995-07-01 00:00:00
abstract::The effects of graded doses of anisotropine methylbromide on nocturanl gastric secretion were investigated in a double-blind crossover study in man. Single doses considerably higher than those usually employed for daytime use in adjunctive therapy of peptic ulcer disease significantly reduced acid secretion without si...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1977.tb04583.x
更新日期:1977-01-01 00:00:00
abstract::The effect of hepatic impairment on the pharmacokinetics of a sustained-release formulation of ranolazine and 3 major metabolites was investigated in an open-label, parallel-group study. Ranolazine (875-mg loading dose followed by 500 mg every 12 hours for a total of 4 maintenance doses) was administered to subjects w...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1177/0091270005276739
更新日期:2005-07-01 00:00:00
abstract::Sirolimus (RAPA) and cyclosporine (CsA) are immunosuppressive compounds that are being used concomitantly in renal transplant patients. Both drugs are dosed orally, have common intestinal and hepatic metabolism and intestinal transport mechanisms, and thus offer potential for pharmacokinetic drug interactions. A singl...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/0091270003257227
更新日期:2003-10-01 00:00:00
abstract::Despite a robust exposure-response relationship of infliximab in inflammatory bowel disease (IBD), attempts to adjust dosing to individually predicted serum concentrations of infliximab (SICs) are lacking. Compared with labor-intensive conventional software for pharmacokinetic (PK) modeling (eg, NONMEM) dashboards are...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1069
更新日期:2018-06-01 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