Journal of Clinical Pharmacology最新文献_第6页

Population pharmacokinetics and pharmacodynamics of brief etomidate infusion in healthy volunteers. 健康志愿者短暂输注依托咪酯的人群药代动力学和药效学。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2011-04-01 Epub Date: 2010-05-24 DOI: 10.1177/0091270010369242

Kotaro Kaneda, Susumu Yamashita, Sukyung Woo, Tae-Hyung Han

{"title":"Population pharmacokinetics and pharmacodynamics of brief etomidate infusion in healthy volunteers.","authors":"Kotaro Kaneda, Susumu Yamashita, Sukyung Woo, Tae-Hyung Han","doi":"10.1177/0091270010369242","DOIUrl":"https://doi.org/10.1177/0091270010369242","url":null,"abstract":"This study established the pharmacokinetic and pharmacodynamic relationships of the bispectral index (BIS) and Observer's Assessment of Alertness/Sedation (OAA/S) scale with effect site drug concentrations during and after brief etomidate infusion. Eighteen American Society of Anesthesiologists status I or II volunteers received etomidate (0.2%) infusion at 5 mg/min until the loss of eyelash reflexes, and spontaneous recovery was allowed. Data for plasma etomidate concentrations, BIS, and OAA/S were collected every minute and analyzed by NONMEM. A 2-compartment pharmacokinetic model and a pharmacodynamic sigmoid E(max) model fit the data best, with volumes of distribution at central and peripheral compartments of 4.45 and 74.90 L, respectively, and systemic and intercompartmental clearances of 0.63 and 3.16 L/min, respectively. t(1/2)k(e0) was 1.550 min. EC(50) values were 0.526 and 0.554 µg/mL, and gamma values were 2.25 and 6.24 for BIS and OAA/S, respectively. The prediction probability between OAA/S and BIS was 0.8. The slopes of the curves suggest that BIS is a better monitor of depth of sedation and hypnosis, whereas OAA/S may be more useful for monitoring sleep versus wakefulness. These results should be interpreted within the context of short-term etomidate infusion of less than 10 minutes.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"51 4","pages":"482-91"},"PeriodicalIF":2.9,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270010369242","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29011200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 23

Pharmacokinetics, safety, and tolerability following multiple oral doses of varenicline under various titration schedules in elderly nonsmokers. 老年非吸烟者在不同滴定方案下多次口服伐尼克兰的药代动力学、安全性和耐受性。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2011-04-01 Epub Date: 2010-05-13 DOI: 10.1177/0091270010370461

Qinying Zhao, Elias Schwam, Terence Fullerton, Melissa O'Gorman, Aaron H Burstein

{"title":"Pharmacokinetics, safety, and tolerability following multiple oral doses of varenicline under various titration schedules in elderly nonsmokers.","authors":"Qinying Zhao, Elias Schwam, Terence Fullerton, Melissa O'Gorman, Aaron H Burstein","doi":"10.1177/0091270010370461","DOIUrl":"https://doi.org/10.1177/0091270010370461","url":null,"abstract":"This study was designed to investigate the multiple-dose pharmacokinetics, safety, and tolerability of the selective α4β2 nicotinic acetylcholine partial agonist, varenicline, in elderly (65-85 years old) nonsmokers. Fifty male and female subjects with normal renal function for their age were randomized to receive varenicline or placebo once or twice daily for 3 weeks in an investigator- and subject-blinded parallel-group design. Treatment regimens included weekly titration (n = 14; days 1-7, 0.5 mg once daily; days 8-14, 0.5 mg twice daily; days 15-21, 1 mg twice daily); 2-week twice-daily titration (n = 13; days 1-14, 0.5 mg once daily; days 15-21, 0.5 mg twice daily); 2-week once-daily titration (n = 13; days 1-14, 0.5 mg once daily; days 15-21, 1 mg once daily); and placebo (n = 10). Approximate dose-proportional increases in systemic exposure of varenicline at steady state, based on maximum concentration and area under the plasma concentration-time curve over the 24-hour period at steady state, were observed across the dose range of 0.5 to 2 mg/d. Median time to maximum concentration was 3 hours. Mean elimination half-life was estimated to be approximately 24 to 32 hours and independent of dose. Varenicline was considered to be safe and well tolerated in this elderly nonsmoking population.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"51 4","pages":"492-501"},"PeriodicalIF":2.9,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270010370461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28985909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Effects of commonly administered agents and genetics on nebivolol pharmacokinetics: drug-drug interaction studies. 常用药物和遗传对奈比洛尔药代动力学的影响:药物-药物相互作用研究。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2011-04-01 Epub Date: 2010-05-20 DOI: 10.1177/0091270010370846

Charles Lindamood, Stephan Ortiz, Andrew Shaw, Russ Rackley, J Christopher Gorski

{"title":"Effects of commonly administered agents and genetics on nebivolol pharmacokinetics: drug-drug interaction studies.","authors":"Charles Lindamood, Stephan Ortiz, Andrew Shaw, Russ Rackley, J Christopher Gorski","doi":"10.1177/0091270010370846","DOIUrl":"https://doi.org/10.1177/0091270010370846","url":null,"abstract":"Drug interactions are a significant clinical concern, particularly in patients with conditions such as heart disease and hypertension, in whom coadministration of multiple drugs is common. Nebivolol is a selective β(1)-blocker with vasodilatory properties approved for the treatment of hypertension. Drug-drug interactions were investigated when nebivolol was coadministered to subjects classified as poor CYP2D6 metabolizers and extensive CYP2D6 metabolizers who were receiving other drugs commonly administered to patients with hypertension or compounds metabolized by cytochrome P450 (CYP) 2D6. There were no drug-drug interactions when nebivolol was coadministered with hydrochlorothiazide, furosemide, ramipril, losartan, digoxin, or warfarin. Coadministration with fluoxetine (also metabolized by CYP2D6) in extensive CYP2D6 metabolizers impeded the apparent clearance of nebivolol. The authors conclude that nebivolol is safe and well tolerated regardless of genotype and type of medication coadministered.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"51 4","pages":"575-85"},"PeriodicalIF":2.9,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270010370846","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29003737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 30

Tecarfarin, a novel vitamin K reductase antagonist, is not affected by CYP2C9 and CYP3A4 inhibition following concomitant administration of fluconazole in healthy participants. 替卡法林是一种新型的维生素K还原酶拮抗剂，在健康受试者同时服用氟康唑后，不受CYP2C9和CYP3A4抑制的影响。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2011-04-01 Epub Date: 2010-07-09 DOI: 10.1177/0091270010370588

Linda M Bavisotto, David J Ellis, Peter G Milner, Daniel L Combs, Ian Irwin, Daniel M Canafax

{"title":"Tecarfarin, a novel vitamin K reductase antagonist, is not affected by CYP2C9 and CYP3A4 inhibition following concomitant administration of fluconazole in healthy participants.","authors":"Linda M Bavisotto, David J Ellis, Peter G Milner, Daniel L Combs, Ian Irwin, Daniel M Canafax","doi":"10.1177/0091270010370588","DOIUrl":"https://doi.org/10.1177/0091270010370588","url":null,"abstract":"Comparative pharmacokinetics of vitamin K epoxide reductase antagonists tecarfarin and warfarin were assessed before and after coadministration for 21 days of the CYP450 inhibitor fluconazole in a randomized, open-label, single-center drug interaction study. Twenty healthy adult participants were randomized 1:1 to receive approximately equipotent single oral doses of tecarfarin (50 mg) or warfarin (17.5 mg). Following 7 days of baseline serial blood level collections, each participant received oral fluconazole 400 mg daily for 21 days. A second identical single oral dose of tecarfarin or warfarin was given 14 days after starting fluconazole with serial pharmacokinetic sampling. Key pharmacokinetic parameters C(max), t(max), AUC(0-168), apparent clearance, and t(1/2) demonstrated no tecarfarin-fluconazole interaction but a strong warfarin-fluconazole interaction. The ratio of log-transformed mean AUC(0-168) with versus without fluconazole for tecarfarin was 91.2% (90% confidence interval [CI]: 83.3-99.8) and for racemic warfarin was 213% (90% CI: 202-226). The 90% CI was entirely within the standard 80% to 125% bioequivalence interval for tecarfarin but well outside the bioequivalence interval for warfarin, confirming a clinically significant pharmacokinetic interaction between warfarin and fluconazole. In contrast, tecarfarin pharmacokinetics were apparently unchanged by fluconazole.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"51 4","pages":"561-74"},"PeriodicalIF":2.9,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270010370588","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29115646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 26

Human breast milk as a source of DNA for amplification. 人类母乳作为DNA扩增的来源。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2011-04-01 Epub Date: 2010-05-24 DOI: 10.1177/0091270010370847

David M Haas, Michael Daum, Todd Skaar, Santosh Philips, Donna Miracle, Jamie L Renbarger

引用次数: 0

Single- and multiple-dose pharmacokinetics of the selective nicotinic receptor partial agonist, varenicline, in healthy Japanese adult smokers. 选择性烟碱受体部分激动剂伐尼克兰在健康日本成年吸烟者中的单剂量和多剂量药代动力学

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2011-04-01 Epub Date: 2010-06-15 DOI: 10.1177/0091270010372388

H Kikkawa, N Maruyama, Y Fujimoto, T Hasunuma

{"title":"Single- and multiple-dose pharmacokinetics of the selective nicotinic receptor partial agonist, varenicline, in healthy Japanese adult smokers.","authors":"H Kikkawa, N Maruyama, Y Fujimoto, T Hasunuma","doi":"10.1177/0091270010372388","DOIUrl":"https://doi.org/10.1177/0091270010372388","url":null,"abstract":"Varenicline is a novel selective α4β2 nicotinic acetylcholine partial agonist developed for smoking cessation. Single- and multiple dose studies were conducted to investigate pharmacokinetics, safety, and tolerability of varenicline in healthy male Japanese smokers. The single-dose study was conducted as a double-blind, placebo-controlled, 4-way crossover study. Subjects received varenicline (0.25, 0.5, 1.0, 2.0 mg) or placebo at an interval of 2 weeks. The double-blind, placebo-controlled multiple-dose study was conducted as 2 cohorts, each consisting of 8 subjects randomized to varenicline tablets twice daily (0.5 or 1.0 mg) and 4 subjects randomized to placebo administered for 14 days. In both studies, varenicline was well tolerated at doses up to and including 2 mg daily. Dose-proportional increases in varenicline systemic exposure were observed following single and multiple dosing. Peak plasma concentrations generally occurred within 2 to 4 hours after dosing. Mean half-life estimates ranged from approximately 13 to 19 hours after single dosing and 24 to 28 hours after repeat dosing. Consistent with this, both 0.5 and 1.0 mg twice daily resulted, on average, in an approximate 3-fold increase in varenicline systemic exposure. These results showed that the single- and multiple-dose pharmacokinetics of varenicline in Japanese smokers were similar to those previously reported in Western smokers.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"51 4","pages":"527-37"},"PeriodicalIF":2.9,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270010372388","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29058399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19

Effect of steady-state enoxacin on single-dose pharmacokinetics of roflumilast and roflumilast N-oxide. 稳态依诺沙星对罗氟司特和罗氟司特n -氧化物单剂量药代动力学的影响。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2011-04-01 Epub Date: 2010-05-13 DOI: 10.1177/0091270010370590

Gezim Lahu, Nassr Nassr, Rolf Herzog, Martin Elmlinger, Peter Ruth, Markus Hinder, Andreas Huennemeyer

{"title":"Effect of steady-state enoxacin on single-dose pharmacokinetics of roflumilast and roflumilast N-oxide.","authors":"Gezim Lahu, Nassr Nassr, Rolf Herzog, Martin Elmlinger, Peter Ruth, Markus Hinder, Andreas Huennemeyer","doi":"10.1177/0091270010370590","DOIUrl":"https://doi.org/10.1177/0091270010370590","url":null,"abstract":"Roflumilast is an oral phosphodiesterase 4 (PDE4) inhibitor for the treatment of chronic obstructive pulmonary disease (COPD). It is metabolized by CYP1A2 and CYP3A4 to its primary metabolite, roflumilast N-oxide, through which >90% total PDE4 inhibitory activity (tPDE4i) is mediated. Fluoroquinolones, of which enoxacin is the most potent CYP1A2 inhibitor, are used to treat COPD exacerbations. This phase I, open, nonrandomized, fixed-sequence, 2-period study evaluated the effects of steady-state enoxacin on the single-dose pharmacokinetics of roflumilast and roflumilast N-oxide. Twenty healthy participants received roflumilast, 500 µg once daily, on days 1 and 12, and enoxacin, 400 mg twice daily, on days 7 to 18. Pharmacokinetic profiles were obtained for days 1 to 6 and 12 to 19. The safety and tolerability of all treatments were also assessed. In 19 evaluable participants, coadministration led to 56% higher mean systemic exposure, 20% higher mean peak concentrations, and 36% lower mean apparent oral clearance compared with roflumilast alone. For roflumilast N-oxide, 23% higher mean systemic exposure and 14% lower mean peak concentrations were seen after coadministration. Roflumilast was well tolerated both alone and in combination with enoxacin. A weak interaction was shown between roflumilast and enoxacin, as mean tPDE4i increased by 25%, but is unlikely to have clinical relevance.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"51 4","pages":"586-93"},"PeriodicalIF":2.9,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270010370590","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28986897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Clonidine clearance matures rapidly during the early postnatal period: a population pharmacokinetic analysis in newborns with neonatal abstinence syndrome. 可乐定清除迅速成熟在出生后早期:人口药代动力学分析与新生儿戒断综合征的新生儿。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2011-04-01 Epub Date: 2010-05-19 DOI: 10.1177/0091270010370587

Hong-Guang Xie, Ying Jun Cao, Estelle B Gauda, Alexander G Agthe, Craig W Hendrix, Howard Lee

{"title":"Clonidine clearance matures rapidly during the early postnatal period: a population pharmacokinetic analysis in newborns with neonatal abstinence syndrome.","authors":"Hong-Guang Xie, Ying Jun Cao, Estelle B Gauda, Alexander G Agthe, Craig W Hendrix, Howard Lee","doi":"10.1177/0091270010370587","DOIUrl":"https://doi.org/10.1177/0091270010370587","url":null,"abstract":"The population pharmacokinetic (PK) profile of oral clonidine was characterized in newborns with neonatal abstinence syndrome, and significant covariates affecting its PK parameters were identified. Plasma clonidine concentration data were obtained from a clinical trial in which 36 newborns, aged 1 to 25 days (postnatal age, PNA) and weighing 2.1 to 3.9 kg, were enrolled to take multiple oral doses of clonidine. The population PK model of clonidine was developed by NONMEM, and significant covariates were identified, followed by nonparametric bootstraps (2000 replicates) and simulation experiments. A 1‐compartment open linear PK model was chosen to describe plasma concentrations of clonidine, and body weight and PNA were significant covariates for apparent clearance (CL/F) as follows: CL/F (L/h) = 15.2 × [body weight (kg)/70]0.75 × [PNA (day)0.441/(4.060.441 + PNA (day)0.441)]. Furthermore, CL/F of clonidine increased rapidly with PNA during the first month of life after body weight was adjusted. Any optimal dosage regimen for clonidine in term neonates should be based on infant's age and body weight, and 1.5 μg/kg every 4 hours is proposed starting the second week of life based on the simulation results.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"51 4","pages":"502-11"},"PeriodicalIF":2.9,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270010370587","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29002476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 43

Betahistine treatment improves the recovery of static symptoms in patients with unilateral vestibular loss. 倍他司汀治疗可改善单侧前庭功能丧失患者静态症状的恢复。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2011-04-01 Epub Date: 2010-10-12 DOI: 10.1177/0091270010369241

Christine Redon, Christophe Lopez, Laurence Bernard-Demanze, Michel Dumitrescu, Jacques Magnan, Michel Lacour, Liliane Borel

{"title":"Betahistine treatment improves the recovery of static symptoms in patients with unilateral vestibular loss.","authors":"Christine Redon, Christophe Lopez, Laurence Bernard-Demanze, Michel Dumitrescu, Jacques Magnan, Michel Lacour, Liliane Borel","doi":"10.1177/0091270010369241","DOIUrl":"https://doi.org/10.1177/0091270010369241","url":null,"abstract":"Vestibular loss induces a combination of postural, oculomotor, and perceptive symptoms that are compensated over time. The aim of this study was to analyze the influence of betahistine dihydrochloride on vestibular compensation. A randomized, double-blind, placebo-controlled study was performed in Menière's disease patients who underwent a curative unilateral vestibular neurotomy (UVN). The effects of betahistine treatment were investigated on a broad spectrum of vestibular-induced changes resulting from vestibular loss: body sway, head orientation, ocular cyclotorsion, spontaneous nystagmus, verticality perception, and self-evaluation of the postural stability. The time course of the recovery was compared in 16 patients who received either a placebo or betahistine (24 mg b.i.d.) from 3 days up to 3 months after UVN. Patients were examined before (day -1) and after UVN (days 7, 30, and 90). Results indicate that betahistine reduces the time to recovery by 1 month or more depending on the tested functions. Betahistine was effective as soon as 4 days after treatment administration, and the effect remained during the whole compensation period (up to 3 months). The observed clinical effects may be attributed to an action of betahistine in rebalancing the neuronal activity between contralateral vestibular nuclei.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"51 4","pages":"538-48"},"PeriodicalIF":2.9,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270010369241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29348580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 47

Lessons learned from the development of oral calcitonin: the first tablet formulation of a protein in phase III clinical trials. 从口服降钙素开发中获得的经验教训:第一个处于III期临床试验的蛋白质片剂配方。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2011-04-01 Epub Date: 2010-07-21 DOI: 10.1177/0091270010372625

M A Karsdal, K Henriksen, A C Bay-Jensen, B Molloy, M Arnold, M R John, I Byrjalsen, M Azria, B J Riis, P Qvist, C Christiansen

{"title":"Lessons learned from the development of oral calcitonin: the first tablet formulation of a protein in phase III clinical trials.","authors":"M A Karsdal, K Henriksen, A C Bay-Jensen, B Molloy, M Arnold, M R John, I Byrjalsen, M Azria, B J Riis, P Qvist, C Christiansen","doi":"10.1177/0091270010372625","DOIUrl":"https://doi.org/10.1177/0091270010372625","url":null,"abstract":"Oral delivery of proteins has been hampered by an array of difficulties. However, promising novel oral delivery systems have been developed. 5-CNAC, formulated with the peptide salmon calcitonin, is in phase III clinical trials for the treatment of osteoporosis or osteoarthritis and could become the first marketed oral peptide. This article reviews key findings and implications from studies undertaken to date with this oral formulation. Findings include these: (1) the optimal calcitonin tablet dose is 0.8 mg; (2) 0.8 mg of oral calcitonin is rapidly absorbed, reaching maximum concentration in 15 to 30 minutes, and is eliminated from plasma with a short half-life-9 to 15 minutes; (3) the 0.8-mg tablet is more highly absorbed than the marketed nasal formulation, with biomarker levels indicating significantly greater efficacy in suppression of bone resorption; (4) drug absorption is increased with dosing at least 10 minutes before a meal rather than postprandially and also with 50 mL of water; (5) the optimal timing of dosing for osteoporosis therapy is in the evening to mitigate the circadian peak in bone resorption; and (6) the oral formulations of synthetic and recombinant calcitonin have similar pharmacokinetic and pharmacodynamic properties. These key findings may aid researchers in the development of other oral formulations.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"51 4","pages":"460-71"},"PeriodicalIF":2.9,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270010372625","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29147734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 86