Pharmacokinetics and pharmacodynamics of immediate-release versus extended-release guanfacine in adult daily smokers
Open accessAbstract
Background: Guanfacine is Food and Drug Administration approved for hypertension and attention-deficit hyperactivity disorder and has been used off-label for migraine prophylaxis, heroin withdrawal, and more recently smoking cessation. Previous studies have shown positive effects of 3 mg/d of immediate-release (IR) guanfacine on smoking outcomes, but the dose equivalency of the IR and extended-release (ER) formulations is unknown. Procedures: A within-subject design was used to compare the pharmacokinetics and pharmacodynamics of 3 mg/d of IR, 4 mg/d of ER, and 6 mg/d of ER guanfacine in adult daily smokers (n = 5). Plasma medication levels, vital signs, cigarettes per day, tobacco craving, and adverse events were assessed. Medication was titrated to stable dosing after each laboratory day (3 mg/d IR, then 4 mg/d ER, then 6 mg/d ER). Results: Plasma medication levels did not differ between the 3 mg/d of IR and 4 mg/d of ER doses after 24 hours from last dose and were highest at the 6 mg/d of ER dose (3 mg/d IR: M = 3.40 ng/mL, SE = 0.34 vs 4 mg/d ER: M = 3.46 ng/mL, SE = 0.67 vs 6 mg/d ER: M = 5.92 ng/mL, SE = 1.02). All doses of guanfacine decreased heart rate and blood pressure from baseline. Absolute values of cigarettes per day (6 mg/d ER) and tobacco craving (4 and 6 mg/d ER) were lowest with the ER formulations. Treatment-emergent adverse events were subject rated as minimal to mild, except dry mouth. Conclusions: We demonstrated similar pharmacokinetic profiles between 3 mg/d of IR guanfacine and 4 mg/d of ER guanfacine, as hypothesized. All doses of guanfacine were well tolerated.
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Extended release guanfacine was more effective than an equivalent dose of immediate release guanfacine.
“The extended release formulation was more effective than an equivalent dose of immediate release guanacine (Verplaetse et al., 2019).”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Verplaetse et al., 2019
The Results section (Cigarettes per day & tobacco craving; page unavailable) reports the lowest absolute craving values with ER guanfacine, but no significant difference in smoking or craving across doses. The Discussion likewise says the study did not demonstrate a significant effect and calls for further study. It compared 3 mg/day IR with 4 and 6 mg/day ER, not equal milligram doses, so the claim of greater effectiveness at an equivalent dose overstates the findings. (LLM, conf=0.88)
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References 11 · Cited by 7
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- Authors
- Verplaetse, T. L., Roberts, W., Moore, K. E., Peltier, M. R., Oberleitner, L. M., & McKee, S. A.
- Affiliations
- Yale University (US)
- Corresponding author
- McKee, Sherry A.
- ORCID
- Venue
- Journal of Clinical Psychopharmacology
- Published
- 2019-03
- Volume
- 39
- Issue
- 2
- Pages
- 124-128
- ISSN
- 0271-0749 (ISSN-L)
- 1533-712X
- PMC
- PMC6391212
- OpenAlex
- W2914513766
- Cited by
- 7
- References
- 11
- Citations by year
- 2026: 2 · 2022: 2 · 2020: 2 · 2019: 1
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (K01AA025670)
- National Institute on Drug Abuse (P50DA033945, R01DA035001)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Keywords
- guanfacine, immediate-release formulation, sustained-release formulation, smoking cessation, pharmacokinetics, pharmacodynamics, plasma drug concentration, cigarette craving, cigarettes per day, blood pressure, heart rate, adverse events, xerostomia
- MeSH terms
- Adult, Blood Pressure, Delayed-Action Preparations, Dose-Response Relationship, Drug, Female, Heart Rate, Humans, Male, Middle Aged, Guanfacine, Smoking Cessation, Treatment Outcome, Adrenergic alpha-2 Receptor Agonists, Drug Liberation
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