Systemic availability and pharmacokinetics of thymol in humans.

Abstract:

:Essential oil compounds such as found in thyme extract are established for the therapy of chronic and acute bronchitis. Various pharmacodynamic activities for thyme extract and the essential thyme oil, respectively, have been demonstrated in vitro, but availability of these compounds in the respective target organs has not been proven. Thus, investigation of absorption, distribution, metabolism, and excretion are necessary to provide the link between in vitro effects and in vivo studies. To determine the systemic availability and the pharmacokinetics of thymol after oral application to humans, a clinical trial was carried out in 12 healthy volunteers. Each subject received a single dose of a Bronchipret TP tablet, which is equivalent to 1.08 mg thymol. No thymol could be detected in plasma or urine. However, the metabolites thymol sulfate and thymol glucuronide were found in urine and identified by LC-MS/MS. Plasma and urine samples were analyzed after enzymatic hydrolysis of the metabolites by headspace solid-phase microextraction prior to GC analysis and flame ionization detection. Thymol sulfate, but not thymol glucuronide, was detectable in plasma. Peak plasma concentrations were 93.1+/-24.5 ng ml(-1) and were reached after 2.0+/-0.8 hours. The mean terminal elimination half-life was 10.2 hours. Thymol sulfate was detectable up to 41 hours after administration. Urinary excretion could be followed over 24 hours. The amount of both thymol sulfate and glucuronide excreted in 24-hour urine was 16.2%+/-4.5% of the dose.

journal_name

J Clin Pharmacol

authors

Kohlert C,Schindler G,März RW,Abel G,Brinkhaus B,Derendorf H,Gräfe EU,Veit M

doi

10.1177/009127002401102678

subject

Has Abstract

pub_date

2002-07-01 00:00:00

pages

731-7

issue

7

eissn

0091-2700

issn

1552-4604

journal_volume

42

pub_type

临床试验,杂志文章
  • Target-Mediated Drug Disposition-A Class Effect of Soluble Epoxide Hydrolase Inhibitors.

    abstract::Pharmacological target-mediated drug disposition (TMDD) represents a special source of nonlinear pharmacokinetics, and its occurrence in large-molecule compounds has been well recognized because numerous protein drugs have been reported to have TMDD due to specific binding to their pharmacological targets. Although TM...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1763

    authors: An G,Lee KSS,Yang J,Hammock BD

    更新日期:2020-10-19 00:00:00

  • A study of the interaction potential of azithromycin and clarithromycin with atorvastatin in healthy volunteers.

    abstract::Atorvastatin is a common option among the HMG-CoA reductase inhibitors for the treatment of lipid disorders because of its excellent lipid-lowering efficacy and overall safety profile. Although these agents can rarely cause rhabdomyolysis by themselves, macrolides, among other agents, have been demonstrated to increas...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Amsden GW,Kuye O,Wei GC

    更新日期:2002-04-01 00:00:00

  • Safety, tolerability, pharmacokinetics, and pharmacodynamic properties of taranabant, a novel selective cannabinoid-1 receptor inverse agonist, for the treatment of obesity: results from a double-blind, placebo-controlled, single oral dose study in health

    abstract::Taranabant is a novel cannabinoid CB-1 receptor (CB1R) inverse agonist in clinical development for the treatment of obesity. This double-blind, randomized, placebo-controlled, single oral dose study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of taranabant (0.5-600 mg) in 24 healthy male...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270008314467

    authors: Addy C,Li S,Agrawal N,Stone J,Majumdar A,Zhong L,Li H,Yuan J,Maes A,Rothenberg P,Cote J,Rosko K,Cummings C,Warrington S,Boyce M,Gottesdiener K,Stoch A,Wagner J

    更新日期:2008-04-01 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

  • The role of the clinical pharmacist in medical education.

    abstract::The clinical pharmacist is an integral member of the Docent team at the University of Missouri--Kansas City School of Medicine with duties in both teaching and patient care. These doctoral-level clinical pharmacists have sole responsibility for providing instruction in basic pharmacology and pharmacokinetics and for t...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1981.tb05700.x

    authors: Covinsky JO

    更新日期:1981-04-01 00:00:00

  • Plasma kinetics, metabolism, and urinary excretion of alpha-lipoic acid following oral administration in healthy volunteers.

    abstract::R(+)-alpha-lipoic acid is a natural occurring compound that acts as an essential cofactor for certain dehydrogenase complexes. The redox couple alpha-lipoic acid/dihydrolipoic acid possesses potent antioxidant activity. Exogenous racemic alpha-lipoic acid orally administered for the symptomatic treatment of diabetic p...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/0091270003258654

    authors: Teichert J,Hermann R,Ruus P,Preiss R

    更新日期:2003-11-01 00:00:00

  • Evaluation of Evolocumab (AMG 145), a Fully Human Anti-PCSK9 IgG2 Monoclonal Antibody, in Subjects With Hepatic Impairment.

    abstract::Evolocumab binds PCSK9, increasing low-density lipoprotein cholesterol (LDL-C) receptors and lowering LDL-C. Target-mediated evolocumab elimination is attributable to PCSK9 binding. As circulating PCSK9 and LDL-C levels are primarily regulated by the liver, we compared evolocumab pharmacokinetics, pharmacodynamics, an...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.832

    authors: Gibbs JP,Slatter JG,Egbuna O,Geller M,Hamilton L,Dias CS,Xu RY,Johnson J,Wasserman SM,Emery MG

    更新日期:2017-04-01 00:00:00

  • Short- and long-term effects of spirapril on renal hemodynamics in patients with essential hypertension.

    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

    authors: Reams GP,Lau A,Knaus V,Bauer JH

    更新日期:1993-04-01 00:00:00

  • CYP2C8*3 polymorphism and donor age are associated with allograft dysfunction in kidney transplant recipients treated with calcineurin inhibitors.

    abstract::Epoxieicosatrienoic acids (EETs) play a protective role against damaging processes in the kidney. We have assessed the effect of polymorphisms in EETs-producing enzymes (CYP2C8 and CYP2J2) and other proteins involved in calcineurin inhibitors (CNIs) disposition (CYP3A4, CYP3A5, and ABCB1) on graft function and clinica...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.15

    authors: Gervasini G,Garcia M,Macias RM,Benitez J,Caravaca F,Cubero JJ

    更新日期:2013-04-01 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

  • Effect of unbound clearance on binding parameters of valproic acid to serum proteins.

    abstract::Nine healthy subjects received 400 mg sodium valproate orally in the fasting state. Binding parameters of valproic acid to serum proteins were determined by Scatchard analysis for individual series of valproic acid data. Total and unbound (intrinsic) clearances (CLt and CLu) were calculated by dividing the dose by the...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1993.tb03932.x

    authors: Kodama Y,Tsutsumi K,Teraoka I,Fujii I,Takeyama M

    更新日期:1993-02-01 00:00:00

  • The effects of epoprostenol on drug disposition. II: A pilot study of the pharmacokinetics of furosemide with and without epoprostenol in patients with congestive heart failure.

    abstract::The effect of epoprostenol on the pharmacokinetics of furosemide was investigated in 23 patients with end-stage congestive heart failure (CHF) receiving conventional therapy alone or conventional therapy plus epoprostenol. Estimates of the apparent oral clearance, volume of distribution, and absorption rate constant f...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1996.tb04196.x

    authors: Carlton LD,Patterson JH,Mattson CN,Schmith VD

    更新日期:1996-03-01 00:00:00

  • Entecavir plus adefovir combination therapy versus lamivudine add-on adefovir for lamivudine-resistant chronic hepatitis B: A meta-analysis.

    abstract::To determine whether adefovir (ADV) in combination with entecavir (ETV) is more effective than with lamivudine (LAM) in patients with lamivudine-resistant chronic HBV infection, electronic databases were searched through May 10th, 2013 to obtain relevant trials which met the inclusion criteria. Meta-analysis was perfo...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,meta分析

    doi:10.1002/jcph.351

    authors: Zeng T,Xu H,Liu JY,Lei Y,Zhong S,Zhou Z

    更新日期:2014-09-01 00:00:00

  • A multivariable analysis of factors governing the steady-state pharmacokinetics of valproic acid in 52 young epileptics.

    abstract::A number of factors have been implicated in the interpatient variability of valproic acid (VPA) pharmacokinetics. These include patient age, concurrent anticonvulsant therapy, and dosage of VPA. In the clinical setting, it is important to determine which of these variables exert a major effect on the observed differen...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1985.tb02836.x

    authors: Hall K,Otten N,Johnston B,Irvine-Meek J,Leroux M,Seshia S

    更新日期:1985-05-01 00:00:00

  • Simultaneous first-order and capacity-limited elimination kinetics after oral administration of verapamil.

    abstract::In this study of the relationship between dose and plasma concentration of verapamil, controlled-release verapamil in doses of 120 mg, 180 mg, 360 mg, and 540 mg were examined. The 48 study subjects received verapamil daily during each of the 4 sequential 5-day dosing segments. Blood samples were collected frequently ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1996.tb04148.x

    authors: Gupta SK,Hwang S,Atkinson L,Longstreth J

    更新日期:1996-01-01 00:00:00

  • An atypical course of neuroleptic malignant syndrome.

    abstract::Based on the discussion of NMS, certain conclusions may be reached in regard to this patient. In the psychiatric setting, agitation and confusion alone are not suggestive of NMS. However in this patient, the symptoms of agitation, the rapid development of EPS symptoms unresponsive to anticholinergic therapy, autonomic...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1994.tb02001.x

    authors: Schneiderhan ME,Marken PA

    更新日期:1994-04-01 00:00:00

  • Model-Based Selection and Recommendation for Subcutaneous Abatacept Dose in Patients With Polyarticular Juvenile Idiopathic Arthritis.

    abstract::The selective T-cell costimulation modulator abatacept is approved for treatment of adult rheumatoid arthritis (RA) and polyarticular juvenile idiopathic arthritis (pJIA; 6-17 years [intravenous] and 2-17 years [subcutaneous]). An extrapolation approach was taken to determine subcutaneous weight-tiered doses of abatac...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1797

    authors: Gandhi Y,Passarell JA,Roy A,Murthy B

    更新日期:2020-12-07 00:00:00

  • The impact of suppressing the renin-angiotensin system on atrial fibrillation.

    abstract::Atrial fibrillation is very common in the United States. After a search of Medline, EMBASE, and CINAHL, 4 trials evaluating inhibitors of the renin-angiotensin system were identified for prevention of new-onset atrial fibrillation, facilitation of electrical cardioversion of atrial fibrillation, and prevention of atri...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,meta分析

    doi:10.1177/0091270005283284

    authors: Kalus JS,Coleman CI,White CM

    更新日期:2006-01-01 00:00:00

  • Increased potency of nondepolarizing relaxants after poliomyelitis.

    abstract::The pathophysiology of poliomyelitis and the recognition of the "post-polio syndrome" suggest that susceptibility to muscle relaxants of patients previously affected by this disease, may be altered. We compared the effects of d-tubocurarine (dTc), pancuronium (P), and gallamine (G) on two pediatric surgical patient gr...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1990.tb03458.x

    authors: Gyermek L

    更新日期:1990-02-01 00:00:00

  • Effects of Corydalis yanhusuo and Angelicae dahuricae on cold pressor-induced pain in humans: a controlled trial.

    abstract::Pain is considered the most common complaint worldwide for which patients seek treatment. Conventional analgesic agents play an important role in modern pain therapy, but they cause several adverse effects. Therefore, newer and better analgesics continue to be investigated. In this controlled clinical trial, the autho...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/0091270004267809

    authors: Yuan CS,Mehendale SR,Wang CZ,Aung HH,Jiang T,Guan X,Shoyama Y

    更新日期:2004-11-01 00:00:00

  • Labetalol in hypertension during the third trimester of pregnancy: its antihypertensive effect and pharmacokinetic-dynamic analysis.

    abstract::The hypotensive effect, kinetics, and concentration-response relationship of labetalol, alpha beta- and alpha 1-adrenoceptor blocking drug, were studied in seven women with a moderate-to-severe hypertension (averaged diastolic blood pressure [DBP] of 100 to 120 mm Hg measured during a 1- to 2-day hospitalization perio...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1993.tb01933.x

    authors: Saotome T,Minoura S,Terashi K,Sato T,Echizen H,Ishizaki T

    更新日期:1993-10-01 00:00:00

  • Effect of Intravenous Alfentanil on Nonpainful Thermally Induced Hyperalgesia in Healthy Volunteers.

    abstract::Experimental interventions that activate specific components of clinical pain are necessary for characterization of underlying mechanisms and pharmacology. Cutaneous hyperalgesia has been described that uses nonpainful heat to induce secondary hyperalgesia. This study evaluated the effect of intravenous alfentanil on ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/jcph.911

    authors: Schifftner C,Schulteis G,Wallace MS

    更新日期:2017-09-01 00:00:00

  • Lack of interaction between lansoprazole and propranolol, a pharmacokinetic and safety assessment.

    abstract::Due to the prevalence of both gastrointestinal and cardiovascular diseases, it is likely that patients may be coprescribed gastric parietal cell proton pump inhibitors and beta-adrenergic antagonists. Therefore, the objectives of this phase I study were to assess the potential effects of the coadministration of lansop...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/00912700022008856

    authors: Karol MD,Locke CS,Cavanaugh JH

    更新日期:2000-03-01 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

  • Correlation of serum creatinine concentration and amikacin half-life.

    abstract::The half-life of amikacin in serum has been measured following the administration of a single intravenous injection of 7 mg/kg in nine adult patients with varying degrees of renal function impairment and in four patients with normal renal function. A linear relationship between the half-life and the serum concentratio...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1975.tb05924.x

    authors: Levy J,Klastensky J

    更新日期:1975-10-01 00:00:00

  • Pharmacokinetics, pharmacodynamics, and safety of microencapsulated octreotide acetate in healthy subjects.

    abstract::The pharmacokinetics, pharmacodynamics, and safety of the marketed formulation of microencapsulated octreotide acetate were evaluated in an open-label study in 22 healthy cholecystectomized subjects. Each subject received a single 30 mg dose of microencapsulated octreotide acetate intramuscularly (i.m.). Concentration...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/00912700022009242

    authors: Chen T,Miller TF,Prasad P,Lee J,Krauss J,Miscik K,Kalafsky G,McLeod JF

    更新日期:2000-05-01 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

  • When are bioavailability studies required? A German proposal.

    abstract::The Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), the German drug regulation authority, issued guidelines for determining whether bioavailability/bioequivalence studies are required for certain drugs. This decision tree is based on pharmacodynamic, pharmacokinetic, and physicochemical criteria. Details ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1998.tb04385.x

    authors: Gleiter CH,Klotz U,Kuhlmann J,Blume H,Stanislaus F,Harder S,Paulus H,Poethko-Müller C,Holz-Slomczyk M

    更新日期:1998-10-01 00:00:00

  • Population pharmacokinetic modeling and simulation of amprenavir following fosamprenavir/ritonavir administration for dose optimization in HIV infected pediatric patients.

    abstract::Fosamprenavir (FPV) is the phosphate ester prodrug of the HIV-1 protease inhibitor amprenavir (APV). A pediatric population pharmacokinetic model for APV was developed and simulation was used to identify dosing regimens for pediatric patients receiving FPV in combination with ritonavir (RTV) which resulted in concentr...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.205

    authors: Barbour AM,Gibiansky L,Wire MB

    更新日期:2014-02-01 00:00:00

  • Pharmacological modulation of peripheral T and B lymphocytes by a selective sphingosine 1-phosphate receptor-1 modulator.

    abstract::CS-0777 is a selective sphingosine 1-phosphate receptor-1 (S1P(1)) modulator under development for treatment of autoimmune conditions. A randomized, double-blind, placebo-controlled study was conducted to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of CS-0777 in escalat...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270011408728

    authors: Moberly JB,Rohatagi S,Zahir H,Hsu C,Noveck RJ,Truitt KE

    更新日期:2012-07-01 00:00:00