Mycophenolate mofetil in islet cell transplant: variable pharmacokinetics but good correlation between total and unbound concentrations.

Abstract:

:The authors investigated the pharmacokinetics of mycophenolic acid over 1 year in 8 Caucasian women undergoing islet cell transplantation. Total mycophenolic acid AUC(0-12) mcg x h/mL before day 60 was 62.1-67.8, declining to 33.6-64.7 thereafter (P = .61). Median total trough concentrations were 1.16-2.90 mcg/mL. Unbound AUC(0-12) was 412-673 ng x h/mL and did not change over time (P = .30). Median percent unbound mycophenolic acid was 0.95% of total concentrations. Individual unbound and total mycophenolic acid concentrations were highly correlated (r2 = 0.94). Total mycophenolic acid trough concentration and total AUC(0-12) were modestly correlated (r2 = 0.65). Intra- and interpatient variability of systemic mycophenolic acid exposure was high. Six patients required dose reductions prior to day 60 due to adverse effects. All subjects achieved insulin independence; 3 later lost graft function. The trend toward higher exposure in the early periods followed by dose reductions suggests that lower initial doses and therapeutic drug monitoring may be necessary.

journal_name

J Clin Pharmacol

authors

Jacobson PA,Green KG,Hering BJ

doi

10.1177/0091270005278599

subject

Has Abstract

pub_date

2005-08-01 00:00:00

pages

901-9

issue

8

eissn

0091-2700

issn

1552-4604

pii

45/8/901

journal_volume

45

pub_type

杂志文章
  • Clinical Comparison of Dexketoprofen Trometamol and Dipyrone in Postoperative Dental Pain.

    abstract::A total of 125 outpatients with moderate to severe pain after surgical removal of one impacted third molar were randomly assigned to receive dexketoprofen trometamol 12.5 or 25 mg or dipyrone 575 mg. For first-dose assessments, patients rated their pain intensity and its relief at regular intervals. From 60 min post d...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1998.38.s1.55

    authors: Bagán JV,López Arranz JS,Valencia E,Santamaría J,Eguidazu I,Horas M,Forns M,Zapata A,Artigas R,Mauleón D

    更新日期:1998-12-01 00:00:00

  • Prediction of overall survival or progression free survival by disease control rate at week 8 is independent of ethnicity: Western versus Chinese patients with first-line non-small cell lung cancer treated with chemotherapy with or without bevacizumab.

    abstract::Categorizations of best response observed at week 8 (between week 3 and 14) of first-line treatment in two studies of bevacizumab plus chemotherapy in Western (878 patients) and Chinese (198 patients) patients with non-small cell lung cancer were assessed together with baseline prognostic factors in multivariate param...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/jcph.191

    authors: Claret L,Gupta M,Han K,Joshi A,Sarapa N,He J,Powell B,Bruno R

    更新日期:2014-03-01 00:00:00

  • Effects of extensive and poor gastrointestinal metabolism on the pharmacodynamics of pravastatin.

    abstract::The enhanced nonenzymatic isomerization of pravastatin to SQ 31,906, a relatively inactive metabolite, has been demonstrated to occur on exposure to gastric acidity in humans. However, the effect of gastric metabolism on the pharmacodynamics of pravastatin has not been studied. In addition, it was hypothesized that so...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1998.tb04432.x

    authors: Ito MK

    更新日期:1998-04-01 00:00:00

  • Protease inhibitors as inhibitors of human cytochromes P450: high risk associated with ritonavir.

    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

    authors: von Moltke LL,Greenblatt DJ,Grassi JM,Granda BW,Duan SX,Fogelman SM,Daily JP,Harmatz JS,Shader RI

    更新日期:1998-02-01 00:00:00

  • Lack of significant effect of bilastine administered at therapeutic and supratherapeutic doses and concomitantly with ketoconazole on ventricular repolarization: results of a thorough QT study (TQTS) with QT-concentration analysis.

    abstract::The effect of bilastine on cardiac repolarization was studied in 30 healthy participants during a multiple-dose, triple-dummy, crossover, thorough QT study that included 5 arms: placebo, active control (400 mg moxifloxacin), bilastine at therapeutic and supratherapeutic doses (20 mg and 100 mg once daily, respectively...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/0091270011407191

    authors: Tyl B,Kabbaj M,Azzam S,Sologuren A,Valiente R,Reinbolt E,Roupe K,Blanco N,Wheeler W

    更新日期:2012-06-01 00:00:00

  • Effects of the orexin receptor antagonist suvorexant on respiration during sleep in healthy subjects.

    abstract::Suvorexant is an orexin receptor antagonist for treating insomnia. The maximum approved dose in the United States and Japan is 20 mg. We evaluated suvorexant effects on respiration during sleep in a randomized, double-blind, 3-period crossover study of healthy adult men (n = 8) and women (n = 4) ≤ 50 years old who rec...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/jcph.523

    authors: Uemura N,McCrea J,Sun H,Donikyan M,Zammit G,Liu R,Louridas B,Marsilio S,Lines C,Troyer MD,Wagner J

    更新日期:2015-10-01 00:00:00

  • Lack of effect of enoximone on the pharmacokinetics of digoxin in patients with congestive heart failure.

    abstract::The aim of this study was to investigate if the concomitant administration of the positive inotropic drug enoximone (100 mg tid) has any effect on the morning through levels of the cardiac glycoside digoxin in 17 patients with congestive heart failure (NYHA II-IV). Plasma concentrations of digoxin were 1.05 +/- 0.37 n...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1990.tb03467.x

    authors: Trenk D,Hertrich F,Winkelmann B,Glauner T,Dieterich HA,Jähnchen E

    更新日期:1990-03-01 00:00:00

  • Comparison of the efficacy and safety of ketorolac and meperidine in the relief of dental pain.

    abstract::A single-dose, randomized, double-blind study of parallel design was conducted to determine the analgesic efficacy and safety of ketorolac tromethamine in patients who experience moderate or severe pain after the surgical removal of three or more third molars, one of which was a bony-impacted mandibular molar. Meperid...

    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.1552-4604.1992.tb03850.x

    authors: Fricke JR Jr,Angelocci D,Fox K,McHugh D,Bynum L,Yee JP

    更新日期:1992-04-01 00:00:00

  • Interactions of clonidine and nifedipine in moderately severe hypertensive patients.

    abstract::In ten patients (age: 47-59 yr) with moderately severe essential hypertension, the humoral and hemodynamic effects of a 4-day therapy with 2 x 75 micrograms clonidine, 2 x 20 mg nifedipine (slow-release), and their combination were investigated and compared with baseline values. The following measurements were observe...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1991.tb03736.x

    authors: Mitrovic V,Patyna W,von Bruchhausen V,Hüting J,Schlepper M

    更新日期:1991-06-01 00:00:00

  • Clinical relevance of cannabis tolerance and dependence.

    abstract::Psychoactive drugs are often widely used before tolerance and dependence is fully appreciated. Tolerance to cannabis-induced cardiovascular and autonomic changes, decreased intraocular pressure, sleep and sleep EEG, mood and behavioral changes is acquired and, to a great degree, lost rapidly with optimal conditions. M...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1981.tb02589.x

    authors: Jones RT,Benowitz NL,Herning RI

    更新日期:1981-08-01 00:00:00

  • Single plasma concentrations of 1'-hydroxymidazolam or the ratio of 1'-hydroxymidazolam:midazolam do not predict midazolam clearance in healthy subjects.

    abstract::The 30-minute ratio of 1'-hydroxymidazolam:midazolam plasma concentrations has been used as a measure of midazolam clearance in liver transplant patients. This study determined if a single concentration of 1'-hydroxymidazolam or the ratio of 1'-hydroxymidazolam:midazolam could be used to predict midazolam clearance in...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/009127002401382614

    authors: Rogers JF,Nafziger AN,Kashuba AD,Streetman DS,Rocci ML Jr,Choo EF,Wilkinson GR,Bertino JS Jr

    更新日期:2002-10-01 00:00:00

  • Effects of antianxiety drug and personality on stress-inducing psychomotor performance test.

    abstract::The present study was carried out to clarify the effects of an antianxiety drug and of personality characteristics on a psychomotor performance test. Forty-eight healthy women college students were chosen from 64 volunteers as having either high or low levels of trait anxiety, neuroticism, or extroversion. Subjects wi...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1978.tb02432.x

    authors: Nakano S,Ogawa N,Kawazu Y,Osato E

    更新日期:1978-02-01 00:00:00

  • Pharmacokinetics and antihypertensive effects of low dose clonidine during chronic therapy.

    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

    authors: Anavekar SN,Howes LG,Jarrott B,Syrjanen M,Conway EL,Louis WJ

    更新日期:1989-04-01 00:00:00

  • Effect of troglitazone on the pharmacokinetics of an oral contraceptive agent.

    abstract::Fifteen healthy women participated in a study to determine the effect of multiple doses of troglitazone on the pharmacokinetics of Ortho-Novum 1/35 (35 micrograms ethinyl estradiol [EE] and 1 mg norethindrone [NE]). Participants received three cycles (21 days each of active drug followed by 7 days without medication) ...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/00912709922007985

    authors: Loi CM,Stern R,Koup JR,Vassos AB,Knowlton P,Sedman AJ

    更新日期:1999-04-01 00:00:00

  • Developmental pharmacokinetic changes of Lamivudine in infants and children.

    abstract::Lamivudine is a nucleoside reverse transcriptase inhibitor widely used in infants and children in combination antiretroviral therapy to treat human immunodeficiency virus (HIV) infection. Developmental changes in lamivudine pharmacokinetic disposition were assessed by combining data from 7 studies of lamivudine (Pedia...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1177/0091270011426563

    authors: Tremoulet AH,Nikanjam M,Cressey TR,Chokephaibulkit K,McKinney R,Mirochnick M,Capparelli EV

    更新日期:2012-12-01 00:00:00

  • Interaction of alcohol and transdermally administered scopolamine.

    abstract::In a placebo-controlled, randomized, double-blind cross-over study in 12 healthy volunteers the effect of acute alcohol intake during treatment with transdermally administered scopolamine (TTS-scopolamine) was investigated. One group of six subjects reached maximal blood alcohol concentrations (BAC) of 80 mg/dL and an...

    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.1552-4604.1988.tb05728.x

    authors: Gleiter CH,Antonin KH,Schoenleber W,Bieck PR

    更新日期:1988-12-01 00:00:00

  • Caffeine metabolism in premature infants.

    abstract::Caffeine has been used frequently in the treatment and prevention of apnea of prematurity. The metabolism of caffeine depends on the activities of the hepatic enzymes that vary from one infant to another. The objective of this study was to determine the influence of postnatal age (PNA), birth weight (BW), study weight...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/00912700122010500

    authors: al-Alaiyan S,al-Rawithi S,Raines D,Yusuf A,Legayada E,Shoukri MM,el-Yazigi A

    更新日期:2001-06-01 00:00:00

  • Electrocardiographic effects of rivastigmine.

    abstract::The electrocardiographic (ECG) effects of rivastigmine treatment were assessed in mild to moderately severe Alzheimer's disease (AD) by analysis of four 26-week, double-blind, multicenter, placebo-controlled, phase III clinical trials. Of an initial 2791 patients, 77% completed treatment. Seventy-one percent required ...

    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:10.1177/00912700222011490

    authors: Morganroth J,Graham S,Hartman R,Anand R

    更新日期:2002-05-01 00:00:00

  • Pharmacokinetics and bioavailability of dilevalol in normotensive volunteers.

    abstract::The bioavailability and pharmacokinetics of dilevalol following oral and intravenous administration were investigated in 12 healthy male volunteers. Dilevalol HCl was administered as a 200-mg oral tablet and a 50-mg intravenous infusion using a randomized cross-over design. Blood and urine samples were collected over ...

    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.1552-4604.1988.tb03189.x

    authors: Kramer WG,Nagabhushan N,Affrime MB,Perentesis GP,Symchowicz S,Patrick JE

    更新日期:1988-07-01 00:00:00

  • Alternative Magnesium Sulfate Dosing Regimens for Women With Preeclampsia: A Population Pharmacokinetic Exposure-Response Modeling and Simulation Study.

    abstract::Magnesium sulfate is the anticonvulsant of choice for eclampsia prophylaxis and treatment; however, the recommended dosing regimens are costly and cumbersome and can be administered only by skilled health professionals. The objectives of this study were to develop a robust exposure-response model for the relationship ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1448

    authors: Du L,Wenning LA,Carvalho B,Duley L,Brookfield KF,Witjes H,de Greef R,Lumbiganon P,Titapant V,Kongwattanakul K,Long Q,Sangkomkamhang US,Gülmezoglu AM,Oladapo OT

    更新日期:2019-11-01 00:00:00

  • Oral antidiabetic drugs: bioavailability assessment of fixed-dose combination tablets of pioglitazone and metformin. Effect of body weight, gender, and race on systemic exposures of each drug.

    abstract::Bioavailability of pioglitazone and metformin, in 2 dose strengths, given either as a fixed-dose combination tablet or as coadministration of commercial tablets (coad), was studied in young healthy subjects in 2 separate studies. In study I (n = 63), single oral doses of 15-mg pioglitazone/500-mg metformin fixed-dose ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,meta分析,随机对照试验

    doi:10.1177/0091270006293755

    authors: Karim A,Slater M,Bradford D,Schwartz L,Zhao Z,Cao C,Laurent A

    更新日期:2007-01-01 00:00:00

  • Pharmacokinetic and pharmacodynamic profiles of CS-518, a selective, long-lasting thromboxane synthase inhibitor, after single and multiple oral administration to healthy volunteers.

    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

    authors: Uematsu T,Nagashima S,Inaba H,Mizuno A,Kosuge K,Nakashima M

    更新日期:1994-01-01 00:00:00

  • Darunavir/ritonavir pharmacokinetics following coadministration with clarithromycin in healthy volunteers.

    abstract::This study investigated the steady-state pharmacokinetic interaction between the HIV protease inhibitor, darunavir (TMC114), administered with low-dose ritonavir (darunavir/ritonavir), and clarithromycin in HIV-negative healthy volunteers. In a 3-way crossover study, 18 individuals received darunavir/ritonavir 400/100...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270007309706

    authors: Sekar VJ,Spinosa-Guzman S,De Paepe E,De Pauw M,Vangeneugden T,Lefebvre E,Hoetelmans RM

    更新日期:2008-01-01 00:00:00

  • Multiple doses of sitagliptin, a selective DPP-4 inhibitor, do not meaningfully alter pharmacokinetics and pharmacodynamics of warfarin.

    abstract::Sitagliptin is an orally active, highly selective dipeptidyl peptidase IV (DPP-4) inhibitor for treatment of type 2 diabetes mellitus. This randomized, open-label, 2-part, 2-period crossover study assessed pharmacokinetics/pharmacodynamics of warfarin in the presence/absence of multiple-dose sitagliptin. Twelve partic...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270009341653

    authors: Wright DH,Herman GA,Maes A,Liu Q,Johnson-Levonas AO,Wagner JA

    更新日期:2009-10-01 00:00:00

  • A computer-based, problem-solving system of instruction in clinical pharmacology.

    abstract::Advances in microcomputer technology provide new ways of incorporating PBL procedures in clinical pharmacology courses. Developments in graphics-user interfaces and analog/digital systems that display physiologic information directly on the monitor enable the computer to serve as a learning resource as laboratory clas...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1991.tb04962.x

    authors: Hutcheon DE,el-Gawly HW

    更新日期:1991-03-01 00:00:00

  • Exposure-dependent inhibition of intestinal and hepatic CYP3A4 in vivo by grapefruit juice.

    abstract::Consumption of typical quantities of grapefruit juice (GFJ) increases the oral bioavailability of several CYP3A4 substrates without affecting their elimination, consistent with selective inhibition of intestinal but not hepatic CYP3A4. However, increases in the AUCs of CYP3A4 substrates recently associated with the co...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/0091270003256059

    authors: Veronese ML,Gillen LP,Burke JP,Dorval EP,Hauck WW,Pequignot E,Waldman SA,Greenberg HE

    更新日期:2003-08-01 00:00:00

  • Tricenter assessment of the efficacy of the ACE inhibitor, moexipril, by ambulatory blood pressure monitoring.

    abstract::To assess the efficacy and time-dependent effects of once-daily moexipril, a nonsulfhydryl ester prodrug of the angiotensin-converting enzyme (ACE) inhibitor, moexiprilat, we conducted a multicenter, double-blind, placebo-controlled trial in 51 hypertensive patients using both clinic and ambulatory blood pressure (BP)...

    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.1552-4604.1995.tb04052.x

    authors: White WB,Whelton A,Fox AA,Stimpel M,Kaihlanen PM

    更新日期:1995-03-01 00:00:00

  • Determination of cefalexin pharmacokinetics and dosage adjustments in relation to renal function.

    abstract::Following oral administration of a single 500-mg dose of cefalexin, serum and urine levels of the antibiotic were determined comparatively in ten normal subjects, ten patients with renal impairment, and ten patients with chronic nephritis on maintenance hemodialysis. In normal subjects, mean serum peak levels (12.0 +/...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1975.tb05918.x

    authors: Brogard JM,Pinget M,Dorner M,Lavillaureix J

    更新日期:1975-10-01 00:00:00

  • Risk-benefit value of inhaled glucocorticoids: a pharmacokinetic/pharmacodynamic perspective.

    abstract::Inhaled glucocorticoids induce therapeutic and adverse systemic effects via the same types of receptors. Analysis of the pharmacokinetic/pharmacodynamic parameters of inhaled glucocorticoids generates a risk-benefit value (RBV). Targeted efficacy with minimal adverse effects helps to quantify an appropriate RBV. High ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1177/0091270003260334

    authors: Rohatagi S,Appajosyula S,Derendorf H,Szefler S,Nave R,Zech K,Banerji D

    更新日期:2004-01-01 00:00:00

  • The absolute bioavailability of oral melatonin.

    abstract::The absolute bioavailability of oral melatonin tablets was studied in 12 normal healthy volunteers. Subjects were administered, in a randomized crossover fashion, melatonin 2 mg intravenously and 2 and 4 mg orally. Blood was sampled over approximately eight (estimated) half-lives. Both the 2 and the 4 mg oral dosages ...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/00912700022009422

    authors: DeMuro RL,Nafziger AN,Blask DE,Menhinick AM,Bertino JS Jr

    更新日期:2000-07-01 00:00:00