Dose escalation pharmacokinetics of intranasal scopolamine gel formulation.

Abstract:

:Astronauts experience Space Motion Sickness requiring treatment with an anti-motion sickness medication, scopolamine during space missions. Bioavailability after oral administration of scopolamine is low and variable, and absorption form transdermal patch is slow and prolonged. Intranasal administration achieves faster absorption and higher bioavailability of drugs that are subject to extrahepatic, first pass metabolism after oral dosing. We examined pharmacokinetics of 0.1, 0.2, and 0.4 mg doses of the Investigational New Drug formulation of intranasal scopolamine gel (INSCOP) in 12 healthy subjects using a randomized, double-blind cross-over study design. Subjects received one squirt of 0.1 g of gel containing either 0.1 mg or 0.2 mg/0.1 mL scopolamine or placebo in each nostril. Serial blood samples and total urine voids were collected after dosing and drug concentrations were determined using a modified LC-MS-MS method. Results indicate dose-linear pharmacokinetics of scopolamine with linear increases in Cmax and AUC within the dose range tested. Plasma drug concentrations were significantly lower in females than in males after administration of 0.4 dose. All three doses were well tolerated with no unexpected or serious adverse side effects reported. These results suggest that intranasal scopolamine gel formulation (INSCOP) offers a fast, reliable, and safe alternative for the treatment of motion sickness.

journal_name

J Clin Pharmacol

authors

Wu L,Boyd JL,Daniels V,Wang Z,Chow DS,Putcha L

doi

10.1002/jcph.391

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

195-203

issue

2

eissn

0091-2700

issn

1552-4604

journal_volume

55

pub_type

杂志文章,随机对照试验
  • Comparison of the stability, efficacy, and adverse effect profile of the innovator 0.005% latanoprost ophthalmic solution and a novel cyclodextrin-containing formulation.

    abstract::Recently, a new latanoprost ophthalmic solution containing cyclodextrins was developed. The purpose of the present work was to compare the stability, clinical efficacy, and adverse effect profile of this formulation with the innovator product. The innovator formulation was stable at 4 degrees C but exhibited degradati...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1177/0091270006292626

    authors: Gonzalez JR,Baiza-Duran L,Quintana-Hau J,Tornero-Montaño R,Castaneda-Hernandez G,Ortiz M,Alarcon-Oceguera F,Beltran-Loustaunau M,Cortez-Gastelum M,Garcidueñas-Mejia J,Gomez-Bastar P,Jimenez-Roman J,Korder-Ortega V,Paczka-Zapata

    更新日期:2007-01-01 00:00:00

  • Intravitreal Injection of a Rho-Kinase Inhibitor (Fasudil) for Recent-Onset Nonarteritic Anterior Ischemic Optic Neuropathy.

    abstract::This study evaluated the effects of intravitreal injection of fasudil (IVF), a Rho-kinase inhibitor, in cases of recent-onset nonarteritic anterior ischemic optic neuropathy (NAION). In this interventional case series, 13 eyes of 13 patients diagnosed with NAION within 14 days of onset were included. The affected eyes...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.655

    authors: Sanjari N,Pakravan M,Nourinia R,Esfandiari H,Hafezi-Moghadam A,Zandi S,Nakao S,Shah-Heidari MH,Jamali A,Yaseri M,Ahmadieh H

    更新日期:2016-06-01 00:00:00

  • Impact of a four-day head-down tilt (-6 degrees) on lidocaine pharmacokinetics used as probe to evaluate hepatic blood flow.

    abstract::The impact of a microgravity simulation using a head-down tilt (-6 degrees) on lidocaine pharmacokinetics used as a probe to evaluate hepatic blood flow is discussed. Eight healthy male subjects were selected for a 7-day study, including a 4-day head-down tilt from day 2 to day 5. Subjects were given 1 mg/kg of lidoca...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1995.tb04110.x

    authors: Saivin S,Pavy-Le Traon A,Cornac A,Güell A,Houin G

    更新日期:1995-07-01 00:00:00

  • Effect of potent CYP2D6 inhibition by paroxetine on atomoxetine pharmacokinetics.

    abstract::The purpose of this study was to characterize the effect of potent CYP2D6 inhibition byparoxetine on atomoxetine disposition in extensive metabolizers. This was a single-blind, two-period, sequential studyin 22 healthy individuals. In period 1, 20 mg atomoxetine bid was administered to steady state. In period 2, 20 mg...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/009127002762491307

    authors: Belle DJ,Ernest CS,Sauer JM,Smith BP,Thomasson HR,Witcher JW

    更新日期:2002-11-01 00:00:00

  • Single- and multiple-dose pharmacokinetics of the selective nicotinic receptor partial agonist, varenicline, in healthy Japanese adult smokers.

    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-blin...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270010372388

    authors: Kikkawa H,Maruyama N,Fujimoto Y,Hasunuma T

    更新日期:2011-04-01 00:00:00

  • Pharmacokinetic interactions of concomitant administration of febuxostat and NSAIDs.

    abstract::To evaluate the effect of febuxostat on the pharmacokinetics of indomethacin and naproxen and vice versa, 2 multiple-dose, 3-period crossover studies were performed in healthy subjects. In study 1, subjects received febuxostat 80 mg once daily, indomethacin 50 mg twice daily, or both. In study 2, subjects received feb...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/0091270006289848

    authors: Khosravan R,Wu JT,Joseph-Ridge N,Vernillet L

    更新日期:2006-08-01 00:00:00

  • 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

  • Different Effects of Atorvastatin on Cardiometabolic Risk Factors in Young Women With and Without Hyperprolactinemia.

    abstract::Long-term prolactin excess is often accompanied by numerous metabolic complications. No previous study has compared the effect of statin therapy on circulating levels of cardiometabolic risk factors in patients with elevated and normal prolactin levels. The study population consisted of 3 age-, weight-, and lipid-matc...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1301

    authors: Krysiak R,Szkróbka W,Okopień B

    更新日期:2019-01-01 00:00:00

  • Safety, tolerability, QTc evaluation, and pharmacokinetics of single and multiple doses of enzastaurin HCl (LY317615), a protein kinase C-beta inhibitor, in healthy subjects.

    abstract::The safety, tolerability, and pharmacokinetics of orally administered enzastaurin were evaluated in 2 placebo-controlled, dose escalation studies in healthy subjects. In the first human dose study, single doses (2-400 mg) were evaluated, with 22 subjects receiving enzastaurin. The mean half-lives of enzastaurin and it...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270007304775

    authors: Welch PA,Sinha VP,Cleverly AL,Darstein C,Flanagan SD,Musib LC

    更新日期:2007-09-01 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

  • 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 pharmaco...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/00912709922007552

    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

    更新日期:1999-01-01 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

  • Population exposure-response model to support dosing evaluation of ixekizumab in patients with chronic plaque psoriasis.

    abstract::Ixekizumab (LY2439821), a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody that selectively binds and neutralizes interleukin (IL) 17A has demonstrated efficacy in the treatment of psoriasis. A population pharmacokinetics-pharmacodynamics model was developed using NONMEM 7.2 to describe the temporal re...

    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.312

    authors: Tham LS,Tang CC,Choi SL,Satterwhite JH,Cameron GS,Banerjee S

    更新日期:2014-10-01 00:00:00

  • Optimization of sampling time for cyclosporine monitoring in transplant patients.

    abstract::Cyclosporine (CsA) dosing is based on CsA plasma or blood concentrations measured 12 to 24 hours after drug administration (trough levels). This study evaluated the relationship between the timing of CsA concentrations and subsequent pharmacokinetic parameters to predict an optimal sampling period. Plasma samples were...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1992.tb03798.x

    authors: Regazzi MB,Rondanelli R,Gastaldi L,Martinelli L,Viganò M

    更新日期:1992-11-01 00:00:00

  • FTY720, a novel immunomodulator in de novo kidney transplant patients: pharmacokinetics and exposure-response relationship.

    abstract::The pharmacokinetics, safety, and preliminary efficacy of FTY720, a novel immunomodulator, were examined in de novo renal transplant patients. Both noncompartmental and population methods were used to estimate pharmacokinetic estimates in the patients. The steady-state plasma concentrations of FTY720 increased in acco...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1177/0091270005279799

    authors: Skerjanec A,Tedesco H,Neumayer HH,Cole E,Budde K,Hsu CH,Schmouder R

    更新日期:2005-11-01 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

  • MAO-B and COMT Genetic Variations Associated With Levodopa Treatment Response in Patients With Parkinson's Disease.

    abstract::The most commonly used Parkinson's disease (PD) treatment is the replacement of dopamine by its levodopa precursor (l-dopa). Monoamine oxidase-B (MAO-B) and catechol-o-methyl transferase (COMT) are enzymes involved in the metabolism and regulation of dopamine availability. In our study we investigated the possible rel...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1096

    authors: Sampaio TF,Dos Santos EUD,de Lima GDC,Dos Anjos RSG,da Silva RC,Asano AGC,Asano NMJ,Crovella S,de Souza PRE

    更新日期:2018-07-01 00:00:00

  • A study of the transplacental transfer and the mammary excretion of cefoxitin in humans.

    abstract::Cefoxitin is a new semisynthetic cephamycin derivative with broad bactericidal activities. In order to determine the extent of the transplacental transfer of cefoxitin, 35 pregnant women received 1 Gm cefoxitin intramuscularly 15 to 180 minutes before normal or Caesarean delivery. Cefoxitin was measured microbiologica...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1981.tb05653.x

    authors: Dubois M,Delapierre D,Chanteux L,Demonty J,Lambotte R,Kramp R,Dresse A

    更新日期:1981-11-01 00:00:00

  • Once-daily trandolapril compared with the twice-daily formulation in the treatment of mild to moderate essential hypertension: assessment by conventional and ambulatory blood pressures.

    abstract::A double-blind, crossover study was carried out to compare the antihypertensive efficacy of the long-acting ACE inhibitor trandolapril 1 mg administered once daily and 0.5 mg twice daily in 31 patients with mild to moderate essential hypertension. After randomization, patients entered a single-blind placebo period of ...

    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.tb01959.x

    authors: Poirier L,Bourgeois J,Lacourcière Y

    更新日期:1993-09-01 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

  • Food effect on bioavailability of modified-release trimetazidine tablets.

    abstract::This study aimed to investigate a food effect on the bio-availability of modified-release (MR) trimetazidine tablets in 36 healthy volunteers. Trimetazidine, an anti-ischemic drug, protects the myocardial cell from the harmful effects of ischemia. The authors investigated the effect of being under a fasting or fed sta...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270011422813

    authors: Ozbay L,Unal DO,Erol D

    更新日期:2012-10-01 00:00:00

  • Effect of Intravenous Oxycodone Versus Sufentanil on the Incidence of Postoperative Nausea and Vomiting in Patients Undergoing Gynecological Laparoscopic Surgery.

    abstract::More than 30% of patients who undergo surgery will experience postoperative nausea and vomiting (PONV) if no prophylactic treatments are used. Although numerous studies have been performed to investigate the factors related to PONV, the effect of perioperative intravenous oxycodone on the incidence of PONV has not bee...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/jcph.1408

    authors: Tao B,Liu K,Wang D,Ding M,Zhao P

    更新日期:2019-08-01 00:00:00

  • PCSK9 Inhibition With Monoclonal Antibodies: Modern Management of Hypercholesterolemia.

    abstract::Current guidelines for hypercholesterolemia treatment emphasize lifestyle modification and lipid-modifying therapy to reduce the risk for cardiovascular disease. Statins are the primary class of agents used for the treatment of hypercholesterolemia. Although statins are effective for many patients, they fail to achiev...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/jcph.766

    authors: Ito MK,Santos RD

    更新日期:2017-01-01 00:00:00

  • Disposition of atorvastatin, rosuvastatin, and simvastatin in oatp1b2-/- mice and intraindividual variability in human subjects.

    abstract::Response to statin therapy is often unpredictable because of variability in metabolism and transport. In the recently created organic anion transporting-polypeptide 1b2 (Oatp1b2/Slco1b2)-null mice, the investigators found significantly lower liver-to-plasma ratios compared with controls for atorvastatin (16.0 ± 5.1 vs...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270011422815

    authors: DeGorter MK,Urquhart BL,Gradhand U,Tirona RG,Kim RB

    更新日期:2012-11-01 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

  • Augmentation of renal citrate excretion by oral potassium citrate administration: time course, dose frequency schedule, and dose-response relationship.

    abstract::The time course, dose frequency schedule, and dose-response relationship of the citraturic response to orally administered potassium citrate was examined in 22 normal volunteers and 21 patients with uric acid or calcium nephrolithiasis. The slow-release (wax matrix) preparation of potassium citrate produced a rapid an...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1984.tb01809.x

    authors: Pak CY,Skurla C,Brinkley L,Sakhaee K

    更新日期:1984-01-01 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

  • Evaluation of sex differences in the pharmacokinetics of ranitidine in humans.

    abstract::A bioequivalence study of two oral formulations of 300 mg ranitidine was carried out in 16 healthy volunteers (8 men and 8 women), and the pharmacokinetics in both sexes were compared. There was bioequivalence of both formulations. The terminal half-life of ranitidine was 7% shorter and the oral apparent clearance 10....

    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.1552-4604.1996.tb04245.x

    authors: Abad-Santos F,Carcas AJ,Guerra P,Govantes C,Montuenga C,Gómez E,Fernández A,Frias J

    更新日期:1996-08-01 00:00:00

  • Ovulation-inhibiting effects of dienogest in a randomized, dose-controlled pharmacodynamic trial of healthy women.

    abstract::Dienogest offers pharmacological advantages for the effective treatment of endometriosis and for use in contraception and hormone replacement therapy. This pharmacodynamic study investigated the ovulation-inhibiting effects of dienogest monotherapy in healthy women. Dienogest was administered at 0.5, 1, 2, or 3 mg dai...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270011423664

    authors: Klipping C,Duijkers I,Remmers A,Faustmann T,Zurth C,Klein S,Schuett B

    更新日期:2012-11-01 00:00:00

  • Identification of the mechanism of action of a glucokinase activator from oral glucose tolerance test data in type 2 diabetic patients based on an integrated glucose-insulin model.

    abstract::A mechanistic drug-disease model was developed on the basis of a previously published integrated glucose-insulin model by Jauslin et al. A glucokinase activator was used as a test compound to evaluate the model's ability to identify a drug's mechanism of action and estimate its effects on glucose and insulin profiles ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270011422231

    authors: Jauslin PM,Karlsson MO,Frey N

    更新日期:2012-12-01 00:00:00