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Pharmacodynamic effects on alertness of single doses of armodafinil in healthy subjects during a nocturnal period of acute sleep loss.
Curr Med Res Opin. 2006 Jan; 22(1):159-67.CM

Abstract

OBJECTIVE

To assess the pharmacodynamics of armodafinil compared with modafinil and placebo on measures of alertness in healthy volunteers undergoing sleep loss.

RESEARCH DESIGN AND METHODS

In a double-blind, active- and placebo-controlled, parallel-group study, 107 healthy male volunteers (aged 18-40 years) were randomized to receive a single oral dose of armodafinil (100, 150, 200, or 300 mg), modafinil (200 mg), or placebo administered at 19:25 h.

MAIN OUTCOME MEASURES

The primary outcome was the Maintenance of Wakefulness Test (MWT), administered every 2 hours from 22:00-08:00 h. Secondary outcomes included the Psychomotor Vigilance Task (PVT) and the Karolinska Sleepiness Scale. Blood samples for pharmacokinetic analysis were collected hourly. Adverse events were evaluated throughout the 2-day laboratory stay and by telephone on day 9.

RESULTS

All four doses of armodafinil, and the dose of 200 mg modafinil, improved wakefulness as measured by increased MWT latencies (treatment effect, p < 0.0001) and reduced PVT lapses of attention (treatment effect, p < 0.0001). The magnitude and duration of these effects at the later time points appeared to be dose and concentration dependent. Armodafinil at 200 mg resulted in comparable C(max), a later t(max), and higher plasma concentrations 6-14 hours post-drug administration than with 200 mg modafinil. Following armodafinil, longer MWT latencies and fewer PVT lapses 6 to approximately 14 hours post-drug administration were observed compared with modafinil. Armodafinil doses were well tolerated, with the most common adverse events including abdominal pain, nausea, and headache. There were reports of tachycardia/palpitations. Decreased mean sleep efficiency and increased mean blood pressure were also observed.

CONCLUSION

Armodafinil improved alertness at all doses studied. Relative to modafinil 200 mg, armodafinil 200 mg showed a comparable peak plasma concentration with higher concentrations 6-14 hours post-drug, and improved wakefulness and sustained attention for a longer time post-dose. Both drugs were well tolerated; however, further research on the efficacy, safety, and tolerability of armodafinil in patients with disorders of excessive sleepiness (ES) is required.

Authors+Show Affiliations

University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA. dinges@mail.med.upenn.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16393442

Citation

Dinges, David F., et al. "Pharmacodynamic Effects On Alertness of Single Doses of Armodafinil in Healthy Subjects During a Nocturnal Period of Acute Sleep Loss." Current Medical Research and Opinion, vol. 22, no. 1, 2006, pp. 159-67.
Dinges DF, Arora S, Darwish M, et al. Pharmacodynamic effects on alertness of single doses of armodafinil in healthy subjects during a nocturnal period of acute sleep loss. Curr Med Res Opin. 2006;22(1):159-67.
Dinges, D. F., Arora, S., Darwish, M., & Niebler, G. E. (2006). Pharmacodynamic effects on alertness of single doses of armodafinil in healthy subjects during a nocturnal period of acute sleep loss. Current Medical Research and Opinion, 22(1), 159-67.
Dinges DF, et al. Pharmacodynamic Effects On Alertness of Single Doses of Armodafinil in Healthy Subjects During a Nocturnal Period of Acute Sleep Loss. Curr Med Res Opin. 2006;22(1):159-67. PubMed PMID: 16393442.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacodynamic effects on alertness of single doses of armodafinil in healthy subjects during a nocturnal period of acute sleep loss. AU - Dinges,David F, AU - Arora,Sanjay, AU - Darwish,Mona, AU - Niebler,Gwendolyn E, PY - 2006/1/6/pubmed PY - 2006/4/21/medline PY - 2006/1/6/entrez SP - 159 EP - 67 JF - Current medical research and opinion JO - Curr Med Res Opin VL - 22 IS - 1 N2 - OBJECTIVE: To assess the pharmacodynamics of armodafinil compared with modafinil and placebo on measures of alertness in healthy volunteers undergoing sleep loss. RESEARCH DESIGN AND METHODS: In a double-blind, active- and placebo-controlled, parallel-group study, 107 healthy male volunteers (aged 18-40 years) were randomized to receive a single oral dose of armodafinil (100, 150, 200, or 300 mg), modafinil (200 mg), or placebo administered at 19:25 h. MAIN OUTCOME MEASURES: The primary outcome was the Maintenance of Wakefulness Test (MWT), administered every 2 hours from 22:00-08:00 h. Secondary outcomes included the Psychomotor Vigilance Task (PVT) and the Karolinska Sleepiness Scale. Blood samples for pharmacokinetic analysis were collected hourly. Adverse events were evaluated throughout the 2-day laboratory stay and by telephone on day 9. RESULTS: All four doses of armodafinil, and the dose of 200 mg modafinil, improved wakefulness as measured by increased MWT latencies (treatment effect, p < 0.0001) and reduced PVT lapses of attention (treatment effect, p < 0.0001). The magnitude and duration of these effects at the later time points appeared to be dose and concentration dependent. Armodafinil at 200 mg resulted in comparable C(max), a later t(max), and higher plasma concentrations 6-14 hours post-drug administration than with 200 mg modafinil. Following armodafinil, longer MWT latencies and fewer PVT lapses 6 to approximately 14 hours post-drug administration were observed compared with modafinil. Armodafinil doses were well tolerated, with the most common adverse events including abdominal pain, nausea, and headache. There were reports of tachycardia/palpitations. Decreased mean sleep efficiency and increased mean blood pressure were also observed. CONCLUSION: Armodafinil improved alertness at all doses studied. Relative to modafinil 200 mg, armodafinil 200 mg showed a comparable peak plasma concentration with higher concentrations 6-14 hours post-drug, and improved wakefulness and sustained attention for a longer time post-dose. Both drugs were well tolerated; however, further research on the efficacy, safety, and tolerability of armodafinil in patients with disorders of excessive sleepiness (ES) is required. SN - 0300-7995 UR - https://www.unboundmedicine.com/medline/citation/16393442/Pharmacodynamic_effects_on_alertness_of_single_doses_of_armodafinil_in_healthy_subjects_during_a_nocturnal_period_of_acute_sleep_loss_ L2 - http://www.tandfonline.com/doi/full/10.1185/030079906X80378 DB - PRIME DP - Unbound Medicine ER -