Pharmacokinetics and tolerability of intravenous trecovirsen (GEM 91), an antisense phosphorothioate oligonucleotide, in HIV-positive subjects.

Abstract:

:Trecovirsen, a 25-mer antisense phosphorothioate oligonucleotide targeted at the gag site of the HIV gene, was administered to HIV-positive volunteers as an i.v. infusion. Single doses ranged from 0.1 to 2.5 mg/kg in an ascending escalation in cohorts of 6 to 12 subjects. Plasma trecovirsen concentrations and pharmacokinetic parameters could be assessed at doses > or = 0.3 mg/kg. Peak plasma concentrations and AUC values increased disproportionately with increasing dose while elimination half-life increased and plasma clearance decreased, indicating a saturable process over this dose range. The only significant adverse event observed was an isolated, transitory increase in activated partial thromboplastin time at doses > or = 2.0 mg/kg that was related to plasma trecovirsen concentrations and is attributed to the polyanionic character of the molecule. Thus, trecovirsen administration was well tolerated in single i.v. doses up to 2.5 mg/kg.

journal_name

J Clin Pharmacol

authors

Séréni D,Tubiana R,Lascoux C,Katlama C,Taulera O,Bourque A,Cohen A,Dvorchik B,Martin RR,Tournerie C,Gouyette A,Schechter PJ

doi

10.1177/00912709922007552

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

47-54

issue

1

eissn

0091-2700

issn

1552-4604

journal_volume

39

pub_type

临床试验,杂志文章
  • The pharmacokinetics of doxylamine: use of automated gas chromatography with nitrogen-phosphorus detection.

    abstract::Sixteen healthy male volunteers received a single oral dose of 25 mg doxylamine succinate. Doxylamine concentrations in plasma were measured by a newly developed gas chromatographic methodology, utilizing direct alkaline extraction into hexane:isoamyl alcohol followed by concentration and autoinjection. Doxylamine kin...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1985.tb02875.x

    authors: Friedman H,Greenblatt DJ

    更新日期:1985-09-01 00:00:00

  • Profile of clinical pharmacologists in the United States.

    abstract::The need for clinical pharmacology in research and education, drug development, and health care delivery is well known. However, a current profile of those working in the field is not available. The ACCP authorized a survey of clinical pharmacologists to provide such a profile. Members of the ACCP or ASCPT were solici...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1989.tb03404.x

    authors: Wilson JT,Brown RD,Kimura KK,Whelton A

    更新日期:1989-08-01 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

  • A phase I clinical trial of aclacinomycin A administered on a five-consecutive-day schedule.

    abstract::In the Phase I study, the new anthracycline aclacinomycin A was given to 22 advanced cancer patients on a schedule of daily intravenous administration for five days repeated every four weeks. The limiting toxicity was myelosuppression, which was severe at a dose of 30 mg/m2 per day for five days. Platelet nadirs were ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1982.tb02686.x

    authors: Woolley PV 3rd,Ayoob MJ,Levenson SM,Smith FP

    更新日期:1982-08-01 00:00:00

  • Clinical utility of ambulatory blood pressure monitoring in target organ complications and equipment choices.

    abstract::Although population studies have demonstrated a relationship between casual office blood pressures and target organ events, the variability of these blood pressure measurements for individual patients has generated an interest in the role of ambulatory blood pressure monitoring for defining the presence of hypertensio...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/j.1552-4604.1992.tb05771.x

    authors: Prisant LM,Bottini PB,Carr AA

    更新日期:1992-07-01 00:00:00

  • Multiple-dose, linear, dose-proportional pharmacokinetics of retigabine in healthy volunteers.

    abstract::Retigabine, a first-in-class selective M-current potassium channel opener, is a novel antiepileptic compound currently in clinical development. The purpose of this randomized placebo-controlled study was to assess retigabine oral safety and pharmacokinetics in healthy male volunteers (N = 45). Subjects received one do...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/00912700222011210

    authors: Ferron GM,Paul J,Fruncillo R,Richards L,Knebel N,Getsy J,Troy S

    更新日期:2002-02-01 00:00:00

  • Magnitude and nature of noncompliance with treatment using isosorbide dinitrate in patients with ischemic heart disease.

    abstract::Isosorbide dinitrate is one of the most commonly prescribed medications for the treatment of ischemic heart disease. It has been demonstrated to be ineffective relative to placebo when taken inappropriately. This study objectively documents the magnitude and nature of compliance in 68 ambulatory patients who were pres...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1996.tb04222.x

    authors: Straka RJ,Fish JT,Benson SR,Suh JT

    更新日期:1996-07-01 00:00:00

  • Long-Term Effect of Rifampicin-Based Anti-TB Regimen Coadministration on the Pharmacokinetic Parameters of Efavirenz and 8-Hydroxy-Efavirenz in Ethiopian Patients.

    abstract::We compared the pharmacokinetic (PK) exposure parameters of efavirenz (EFV) and its major inactive metabolite, 8-hydroxy-efavirenz (8-OH-EFV), in an open-label, single-sequence, and parallel design of HIV-infected and tuberculosis (TB)-HIV-coinfected Ethiopian patients in the HIV-TB Pharmagene study with 20 and 33 pat...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1002/jcph.756

    authors: Habtewold A,Aklillu E,Makonnen E,Amogne W,Yimer G,Aderaye G,Bertilsson L,Owen JS,Burhenne J

    更新日期:2016-12-01 00:00:00

  • Clinical evaluation of hypnotic drugs: contributions from sleep laboratory studies.

    abstract::The most thorough and clinically relevant approach to hypnotic drug evaluation is one that balances the strengths and weaknesses of clinical trials and sleep laboratory evaluations. Advantages of clinical trials include the ability to evaluate large numbers of subjects and specific target groups and to thoroughly asse...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,评审

    doi:10.1002/j.1552-4604.1979.tb02489.x

    authors: Kales A,Scharf MB,Soldatos CR,Bixler EO

    更新日期:1979-07-01 00:00:00

  • Differential influence of two cyclosporine formulations on everolimus pharmacokinetics: a clinically relevant pharmacokinetic interaction.

    abstract::Everolimus is an immunosuppressant intended for use with cyclosporine in acute-rejection prophylaxis following organ transplantation. The possibility of a drug interaction of cyclosporine on everolimus was assessed. In this randomized, two-period, crossover study, 24 healthy subjects received a single oral dose of 2 m...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/0091270002042001011

    authors: Kovarik JM,Kalbag J,Figueiredo J,Rouilly M,Frazier OL,Rordorf C

    更新日期:2002-01-01 00:00:00

  • Extrapolation of Adult Efficacy to Pediatric Patients With Chemotherapy-Induced Nausea and Vomiting.

    abstract::Chemotherapy-induced nausea and vomiting (CINV) is a common treatment-related adverse event that negatively impacts the quality of life of cancer patients. During pediatric drug development, extrapolation of efficacy from adult to pediatric populations is a pathway that can minimize the exposure of children to unneces...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1577

    authors: Momper JD,Heinrichs MT,Krudys K,Griebel D,Kumar S,Kim I,Mehrotra N,Mulberg AE,Garimella N,Nelson R,Reaman G,Sinha V,Yao L,Zineh I,Burckart G,Sachs H,Mulugeta Y

    更新日期:2020-06-01 00:00:00

  • Influence of Panax ginseng on cytochrome P450 (CYP)3A and P-glycoprotein (P-gp) activity in healthy participants.

    abstract::A number of herbal preparations have been shown to interact with prescription medications secondary to modulation of cytochrome P450 (CYP) and/or P-glycoprotein (P-gp). The purpose of this study was to determine the influence of Panax ginseng on CYP3A and P-gp function using the probe substrates midazolam and fexofena...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/0091270011407194

    authors: Malati CY,Robertson SM,Hunt JD,Chairez C,Alfaro RM,Kovacs JA,Penzak SR

    更新日期:2012-06-01 00:00:00

  • The pharmacokinetics of sodium oxybate oral solution following acute and chronic administration to narcoleptic patients.

    abstract::This trial was conducted to evaluate the pharmacokinetics and safety of a sodium oxybate (gamma-hydroxybutyrate [GHB]) oral solution in narcoleptic patients after acute and chronic treatment. An open-label, two-period, two-treatment study design was used. Trial subjects included 13 patients with polysomnographically c...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/0091270003262795

    authors: Borgen LA,Okerholm RA,Lai A,Scharf MB

    更新日期:2004-03-01 00:00:00

  • Biological activity of cannabichromene, its homologs and isomers.

    abstract::Cannabichromene (CBC) is one of four major cannabinoids in Cannabis sativa L. and is the second most abundant cannabinoid in drug-type cannabis. Cannabichromene and some of its homologs, analogs, and isomers were evaluated for antiinflammatory, antibacterial, and antifungal activity. Antiinflammatory activity was eval...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1981.tb02606.x

    authors: Turner CE,Elsohly MA

    更新日期:1981-08-01 00:00:00

  • Feasibility of a breath test for monitoring adherence to vaginal administration of antiretroviral microbicide gels.

    abstract::Adherence to microbicide gel use is critical to optimizing effectiveness in preventing human immunodeficiency virus transmission. The authors hypothesized that ester taggants added to vaginal gels would generate exhaled alcohol and ketone metabolites and provide a "breath test" for vaginal gel use. This 2-arm (vaginal...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270011434157

    authors: Morey TE,Wasdo S,Wishin J,Quinn B,van der Straten A,Booth M,Gonzalez D,Derendorf H,Melker RJ,Dennis DM

    更新日期:2013-01-01 00:00:00

  • Interrelationships among thiazide diuretics and calcium, magnesium, sodium, and potassium balance in normal and hypertensive man.

    abstract::The benzothiadiazide diuretics are known to cause magnesium and potassium wasting and retention of calcium and uric acid. The effect of magnesium replacement on diuretic-induced changes in sodium, potassium, calcium, and magnesium balance, weight, and blood pressure was studied in 12 normal subjects and 13 hypertensiv...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1978.tb01582.x

    authors: Sullivan JM,Dluhy RG,Wacker WE,Solomon HS,Williams GH,Samaha JK

    更新日期:1978-11-01 00:00:00

  • Prolonged accumulation of diazepam in obesity.

    abstract::Six obese (mean weight 92 kg) and five normal (60 kg) subjects received 2 mg diazepam nightly for 30 nights. Determination of diazepam and desmethyldiazepam plasma concentrations during the dosing period and for a withdrawal period indicated that accumulation half-life for both diazepam (7.8 days in obese vs. 3.1 days...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1983.tb02750.x

    authors: Abernethy DR,Greenblatt DJ,Divoll M,Shader RI

    更新日期:1983-08-01 00:00:00

  • 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. Unb...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270005278599

    authors: Jacobson PA,Green KG,Hering BJ

    更新日期:2005-08-01 00:00:00

  • The Bial 10-2474 Phase 1 Study-A Drug Development Perspective and Recommendations for Future First-in-Human Trials.

    abstract::BIA 10-2474 (a fatty acid amide hydrolase inhibitor) was evaluated in a first-in-human phase 1 study in normal volunteers to assess safety/tolerability, pharmacokinetics, pharmacodynamics, and food effect. The dose-escalation process consisted of a single-ascending-dose phase (SAD) and multiple-ascending-dose phase (M...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/jcph.889

    authors: Chaikin P

    更新日期:2017-06-01 00:00:00

  • Postabsorption concentration peaks with brand-name and generic verapamil: a double-blind, crossover study in elderly hypertensive patients.

    abstract::The pharmacokinetic actions, bioequivalence, and cardiovascular effects of two verapamil products were studied in a randomized, double-blind, crossover study in eight elderly hypertensive patients (median age, 69.5 years; range, 60-79 years) given brand-name or generic immediate-release verapamil in 120-mg twice-daily...

    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.1552-4604.1997.tb04331.x

    authors: Saseen JJ,Porter JA,Barnette DJ,Bauman JL,Zajac EJ Jr,Carter BL

    更新日期:1997-06-01 00:00:00

  • Cytochrome P450 Genetic Variations Can Predict mRNA Expression, Cyclophosphamide 4-Hydroxylation, and Treatment Outcomes in Chinese Patients With Non-Hodgkin's Lymphoma.

    abstract::To investigate the impact of cytochrome P450 (CYP) genetic polymorphisms CYP2B6, CYP2C19, and CYP3A5 on mRNA expression, cyclophosphamide/4-hydroxycyclophosphamide pharmacokinetics, and treatment outcomes of the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in Chinese patients ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.878

    authors: Shu W,Chen L,Hu X,Zhang M,Chen W,Ma L,Liu X,Huang J,Pang T,Li J,Zhang Y

    更新日期:2017-07-01 00:00:00

  • Effect of micronization on the bioavailability and pharmacologic activity of spironolactone.

    abstract::The bioavailability and pharmacologic activity of tablets containing micronized spironolactone chemical (median particle size 2.21 micrometers) were compared to those of tablets made from standard spironolactone chemical (median particle size 78.8 micrometers) in healthy men. Apart from particle size, all features of ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1982.tb02694.x

    authors: McInnes GT,Asbury MJ,Ramsay LE,Shelton JR,Harrison IR

    更新日期:1982-08-01 00:00:00

  • Effect of hypothermia and sampling site on blood esmolol concentrations.

    abstract::Esmolol hydrochloride was administered by constant-rate continuous infusion to 10 patients undergoing hypothermic cardiopulmonary bypass for coronary artery revascularization surgery. After a suitable loading dose, the esmolol infusion was started approximately 30 minutes before bypass and was stopped 10 minutes after...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1993.tb04670.x

    authors: Jacobs JR,Croughwell ND,Goodman DK,White WD,Reves JG

    更新日期:1993-04-01 00:00:00

  • Pharmacokinetic and pharmacodynamic profiles of vapiprost, a selective, long-lasting thromboxane receptor antagonist, after single and multiple oral administration to healthy volunteers.

    abstract::A selective thromboxane A2 (TXA2) receptor blocking agent, vapiprost, was orally administered to healthy male Japanese volunteers to investigate the pharmacokinetic and pharmacodynamic properties. The time-profile of vapiprost concentration in plasma was determined and the effects of the drug on platelet aggregation i...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1991.tb01917.x

    authors: Uematsu T,Nagashima S,Mizuno A,Hirano K,Nakashima M

    更新日期:1991-09-01 00:00:00

  • Hypotension and bradycardia in a healthy volunteer following a single 5 mg dose of olanzapine.

    abstract::Olanzapine is an atypical antipsychotic medication indicated for the treatment of schizophrenia and other manifestations of psychotic illness. Common side effects include somnolence, constipation, weight gain, and postural hypotension. The authors report a case of hypotension accompanied by bradycardia in a normal, he...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270002042001013

    authors: Markowitz JS,DeVane CL,Boulton DW,Liston HL,Risch SC

    更新日期:2002-01-01 00:00:00

  • Effects of protriptyline and perphenazine in neurotic depressed outpatients.

    abstract::A four-week comparison of protriptyline 10 mg three times a day and perphenazine 2 mg three times a day, alone and in combination, and a placebo in a group of nonpsychotic depressed outpatients showed no significant differences among any of the treatment groups after both two and four weeks, and a slight trend in favo...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1975.tb02382.x

    authors: Weinstock R,Fisher S,Spillane J,Ise C,Shaw D,Torop P

    更新日期:1975-08-01 00:00:00

  • Which studies of therapy merit credence? Vitamin E and estrogen therapy as cautionary examples.

    abstract::A vast and continuously growing amount of material on drugs exists in the literature to read and evaluate. Frequently, the papers and their recommendations are conflicting and contradictory. Readers are faced with the dilemma of deciding what to believe. The need for evidence-based medicine as a foundation for optimal...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:

    authors: Spector R,Vesell ES

    更新日期:2002-09-01 00:00:00

  • Population Pharmacokinetics of an Intranasally Administered Combination of Oxymetazoline and Tetracaine in Healthy Volunteers.

    abstract::The primary objective of the current investigation was to establish the pharmacokinetic characteristics of oxymetazoline and tetracaine's primary metabolite, para-butylaminobenzoic acid (PBBA), after the intranasal administration of oxymetazoline/tetracaine. Thirty-six subjects contributing a total of 1791 plasma conc...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.799

    authors: Cacek AT,Gobburu JV,Gopalakrishnan M

    更新日期:2017-02-01 00:00:00

  • Pharmacogenetic Analysis of OATP1B1, UGT1A1, and BCRP Variants in Relation to the Pharmacokinetics of Letermovir in Previously Conducted Clinical Studies.

    abstract::The cytomegalovirus (CMV) viral terminase inhibitor letermovir is indicated for prevention of CMV infection in CMV-seropositive allogeneic hematopoietic stem cell transplant recipients. In this analysis, functional variants in solute carrier organic anion transporter family member 1B1 (SLCO1B1), uridine diphosphate-gl...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1420

    authors: Kobie J,Guo Z,Cho CR,Menzel K,McCrea JB,Blanchard R,Shaw PM

    更新日期:2019-09-01 00:00:00

  • Pharmacokinetics of ibuprofen enantiomers in children with cystic fibrosis.

    abstract::Chiral inversion of R(-)- to S(+)-ibuprofen in children with cystic fibrosis was investigated. Children with cystic fibrosis (n = 38, ages 2-13 years) were administered a single oral dose of racemic ibuprofen (20 mg/kg), and the pharmacokinetics of ibuprofen was found to be stereoselective. Mean Cmax, AUC, apparent CL...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/00912700022009594

    authors: Dong JQ,Ni L,Scott CS,Retsch-Bogart GZ,Smith PC

    更新日期:2000-08-01 00:00:00