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 experimental cutaneous hyperalgesia created using this method. Eighteen subjects participated in a randomized, double-blinded, placebo-controlled crossover study consisting of 2 sessions, 1 with alfentanil and 1 with placebo. Using a computer-controlled infusion pump, alfentanil or matching placebo was maintained at a constant plasma level of 75 ng/mL for 1 hour followed by the application of a 40°C heat stimulus to the right thenar eminence for 15 minutes. The temperature was raised by 1°C every 15 minutes until the subject reported pain or 45°C was reached. After the end point was reached, the temperature was maintained, and repeat testing was performed. The nonpainful heat created an area of secondary cutaneous hyperalgesia and significant decrease in mechanical pain threshold on heat-treated right vs untreated left during placebo administration. Alfentanil prevented the hypersensitivity when compared to placebo (P < .05) but failed to reduce the area of secondary hyperalgesia created by nonpainful heat when compared to placebo (P = .06). Neither alfentanil nor the heat lamp treatment showed any significant effect on other neurosensory measures. This study demonstrated a reliable production of cutaneous hyperalgesia using a nonpainful stimulus that is affected by the systemic delivery of alfentanil. This model for human cutaneous experimental pain may be a useful method for scientific characterization of analgesics.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Schifftner C,Schulteis G,Wallace MSdoi
10.1002/jcph.911subject
Has Abstractpub_date
2017-09-01 00:00:00pages
1207-1214issue
9eissn
0091-2700issn
1552-4604journal_volume
57pub_type
杂志文章,随机对照试验abstract：:Traditionally, plasma or serum drug concentrations have been used for the assessment of bioavailability and bioequivalence. Since in the majority of cases the site of drug action is in the tissue rather than the blood, the use of corresponding free, unbound concentrations in the tissue is a much more meaningful approa...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1177/0091270007312152
更新日期：2008-03-01 00:00:00
abstract：:A physiologically based pharmacokinetic model (PBPK) was built for citalopram using Simcyp-based absorption, distribution, metabolism, and excretion simulator. Various physicochemical properties of citalopram were obtained from the published literature. The in vitro-in vivo extrapolation method was used to predict cle...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1541
更新日期：2020-04-01 00:00:00
abstract：:The most recent International Conference on Harmonisation E14 Q&A document states that a separate positive control would not be necessary provided sufficiently high exposures are achieved in the early-phase studies. Realistically, a phase 1 study is unlikely to include a pharmacological positive control, and in cases ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.975
更新日期：2018-01-01 00:00:00
abstract：:Udenafil, a cyclic guanosine monophosphate-specific phosphodiesterase type 5 inhibitor, has been developed to treat erectile dysfunction. We evaluated the effect of age on the pharmacokinetics and tolerability of udenafil. A single-center, open-label, parallel-group phase 1 study was conducted in healthy adult subject...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.739
更新日期：2016-11-01 00:00:00
abstract：:The pharmacokinetic profile of solifenacin succinate (YM905; Vesicare), a new once-daily bladder-selective muscarinic receptor antagonist, was examined in 2 controlled trials of healthy young men. A single-dose study evaluated 5-, 10-, 20-, 40-, 60-, 80-, and 100-mg doses. A multidose study evaluated 5-, 10-, 20-, and...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/0091270004267592
更新日期：2004-09-01 00:00:00
abstract：:In this investigation, the pharmacokinetic and pharmacodynamic properties were determined of multiple doses of sublingual tablets containing either buprenorphine alone or buprenorphine and naloxone. Subjects were experienced opiate users who received escalating doses (4-24 mg) of buprenorphine either alone or in combi...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270005284192
更新日期：2006-02-01 00:00:00
abstract：:This study was designed to evaluate the steady-state pharmacokinetics (PK) of estradiol and its metabolites, estrone and estrone sulfate, following application of a novel estradiol transdermal spray to healthy postmenopausal women. Participants were randomly assigned in parallel to receive 1-, 2-, or 3-spray doses (24...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270009339187
更新日期：2009-09-01 00:00:00
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：
更新日期：2002-09-01 00:00:00
abstract：:The pharmacokinetic characteristics of a slow-release formulation of clonidine (150 micrograms) were compared with those of a conventional formulation (75 micrograms) after acute and chronic (2 week) administration to 12 hypertensive subjects. The Tmax of the slow-release formulation was significantly later than for t...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1992.tb03858.x
更新日期：1992-05-01 00:00:00
abstract：:Inflammatory conditions, such as rheumatoid arthritis, reduce response to calcium channel and beta-adrenergic antagonists but not the angiotensin II type 1 receptor (AT(1)R) antagonist valsartan. Inflammation also reduces clearance of some drugs or active metabolite, thereby reducing response. Active (n = 14) and cont...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270006292163
更新日期：2006-11-01 00:00:00
abstract：:As part of a clinical trial investigating the level of nicotine replacement with different doses of transdermal therapy for smoking cessation, urine excretion rates of nicotine and cotinine were measured in 70 subjects while they were actively smoking (baseline) and for 6 consecutive inpatient days while they were rec...
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.1552-4604.1998.tb05788.x
更新日期：1998-06-01 00:00:00
abstract：:Two once-daily rivaroxaban dosing regimens were compared with warfarin for stroke prevention in patients with non-valvular atrial fibrillation in ROCKET AF: 20 mg for patients with normal/mildly impaired renal function and 15 mg for patients with moderate renal impairment. Rivaroxaban population pharmacokinetic (PK)/p...
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.288
更新日期：2014-08-01 00:00:00
abstract：:Supine office blood pressures (SOBP) and 24-hour automated ambulatory blood pressure monitorings (AABPM) showed blood pressure reductions from a stable baseline to active treatment with 120-, 240-, and 480-mg doses of a new verapamil QD capsule (solid-spheroidal-oral once-daily drug-absorption system: (SODAS) in patie...
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.1552-4604.1991.tb03698.x
更新日期：1991-02-01 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：: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
更新日期：1992-04-01 00:00:00
abstract：:This study aimed to evaluate the safety and tolerability of intravenous (IV) levetiracetam (LEV) as a monotherapy in children aged 1 month-16 years and to explore the pharmacokinetics (PK) of IV LEV and the time to seizure after IV then oral administration of LEV in pediatric children with epilepsy. Children diagnosed...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/jcph.1282
更新日期：2018-12-01 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：:We aim to evaluate the influence of covariates, including cytochrome P450 3A (CYP3A) genetic polymorphisms, on the pharmacokinetics of midazolam (MDZ) in Asian cancer patients, using a population pharmacokinetic approach. Pharmacokinetic data were obtained from 24 adult cancer patients who received an intravenous bolu...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/jcph.230
更新日期：2014-02-01 00:00:00
abstract：:The plasma and red blood cell pharmacokinetics and bioavailability of the natural source (RRR, d) and all racemic (all rac, dl) stereoisomers of alpha-tocopherol were studied in 12 men in a double-blind randomized crossover study. Subjects were administered two 400-mg soft-gelatin capsules of either RRR or all rac alp...
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.1552-4604.1993.tb03909.x
更新日期：1993-01-01 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：:Steady state pharmacokinetics, absolute bioavailability, and dose proportionality of cefepime were evaluated in healthy male subjects after single (250, 500, 1000, or 2000 mg) and multiple (1000 mg every 12 hours for 10 days) intramuscular injections. Safety and tolerance were also monitored. High performance liquid c...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1990.tb03569.x
更新日期：1990-10-01 00:00:00
abstract：:Peginterferon beta-1a was efficacious in a Phase 3 relapsing multiple sclerosis trial, and its safety profile was consistent with other beta interferons. This study evaluated the impact of renal impairment on the pharmacokinetics and pharmacodynamics (neopterin elevation; a biomarker of pharmacological activity induce...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1002/jcph.390
更新日期：2015-02-01 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：:Sustained-release (SR) bupropion (Zyban) is approved as a smoking cessation aid for adults. Since smoking often begins in adolescence, we determined the single-dose pharmacokinetics of bupropion SR in 75 adolescent subjects ranging from 13 to 18 years old. Subjects self-reported their smoking status. Urinary cotinine ...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/00912700122010564
更新日期：2001-07-01 00:00:00
abstract：:The primary albumin binding site of indomethacin is remote from the bilirubin binding site. Indomethacin is, at most, a weak displacer of bilirubin at low serum drug concentrations. When administered at dosages less than 1 mg/kg, indomethacin would appear to be safe with respect to serum binding of bilirubin in premat...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1978.tb01575.x
更新日期：1978-10-01 00:00:00
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
更新日期：2019-09-01 00:00:00
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
更新日期：2013-01-01 00:00:00
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
更新日期：2008-04-01 00:00:00
abstract：:The isoproterenol sensitivity (dose-response curve) and the total body clearance of propranolol were measured in 80 men including 15 normal subjects and 65 essential hypertensive patients (20 borderline and 45 permanent hypertensives). The critical dose of isoproterenol was found to be directly correlated to weight (P...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1976.tb01514.x
更新日期：1976-04-01 00:00:00
abstract：:This open-label study evaluated apixaban pharmacokinetics, pharmacodynamics, and safety in subjects with mild, moderate, or severe renal impairment and in healthy subjects following a single 10-mg oral dose. The primary analysis determined the relationship between apixaban AUC∞ and 24-hour creatinine clearance (CLcr )...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.633
更新日期：2016-05-01 00:00:00
