Solvay Pharmaceuticals, Inc announced the results of a Phase I study evaluating the safety and tolerability of pulmonary dronabinol administered in a one-time dose using a pressurized metered dose inhaler. Dronabinol is a synthetic version of delta-9-tetrahydrocannabinol, which is one of more than 400 compounds found in the marijuana plant (Cannabis sativa L). The research was presented at the American Academy of Neurology (AAN) Annual Meeting in Miami, Fla.

The study found the new formulation of pulmonary dronabinol, delivered with a pressurized metered dose inhaler, provided rapid systemic absorption. All dose levels used in the research were considered safe in healthy young and elderly subjects.

Dronabinol currently is available as an oral capsule, marketed under the trade name MARINOL?.

?Solvay Pharmaceuticals is leading the way in research of pharmaceutical quality cannabinoids as well as alternative drug delivery systems to help provide physicians and patients with new options for treating difficult symptoms,? said Harold H. Shlevin, Ph.D., president and CEO of Solvay Pharmaceuticals, Inc. ?Pulmonary dronabinol has potential application in a variety of conditions, such as the treatment of migraines, nausea, pain management and spasticity in patients with multiple sclerosis.?

In mid-2005, Solvay Pharmaceuticals will launch a proof-of-principle clinical trial to evaluate the efficacy, safety and tolerability of pulmonary dronabinol delivered with a pressurized metered dose inhaler versus placebo for the acute treatment of a single moderate to severe migraine headache attack.

?Some oral medications are broken down by the liver before reaching the bloodstream, which limits the amount of the parent drug that is systemically available,? said Jodi Miller, Pharm.D., M.S., Solvay Pharmaceuticals, Inc. ?The dronabinol metered dose inhaler provides maximum plasma concentrations within minutes, delivers a controlled dose and could offer an alternative for patients when a fast onset of action is desirable.?

About the Study

A randomized, placebo-controlled study of 27 subjects was conducted to evaluate the pharmacokinetics, pharmacodynamics, safety and tolerability of pulmonary dronabinol after single dose administration via a pressurized metered dose inhaler. The population was divided into healthy men 18 to 45 years of age and men and women 65 to 80 years of age.

Doses of dronabinol ranged from 0.3 mg to 9.6 mg in subjects 18 to 45 years. Subjects 65 to 80 years received either 3.6 mg or placebo. Plasma concentrations reached maximum levels (Tmax) within 2 to 7 minutes across all dose levels.

Cognitive functional impairment and Bond-Lader Visual Analogue Scales (VAS) evaluation findings were minimal at doses up to 3.6 mg in both young and elderly subjects. At dose levels of 7.2 mg and higher in the young subjects, cognitive test battery results indicated moderate cognitive functional impairment and VAS declined in self-rated alertness, contentment and calmness. A dose-dependent increase in heart rate was observed for 5 minutes after 0.3 mg and 1 to 4 hours after 9.6 mg. In elderly subjects, the magnitude and duration of the heart rate increase was less compared to young participants. The most common adverse events included cough, somnolence and dizziness.

About Cannabinoids

Dronabinol, a cannabinoid, is part of a class of compounds called CB1/CB2 receptor agonists. Dronabinol and other cannabinoids bind to the CB1 and CB2 receptors in the endogenous cannabinoid system, a unique biological pathway involved in regulating nausea, vomiting, appetite, and other physiologic processes. Concentrations of these receptors exist in many brain regions, including the cerebral cortex, hypothalamus, cerebellum, brainstem and the vomiting center located in the medulla.1


MARINOL? (dronabinol) CIII Capsules is the only U.S. FDA-approved synthetic cannabinoid and is used for the treatment of anorexia associated with weight loss in patients with AIDS and for the treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. MARINOL? is contraindicated in any patient who has a history of hypersensitivity to any cannabinoid or sesame oil. MARINOL? should be used with caution in patients with cardiac disorders; in patients with a history of substance abuse (including alcohol abuse or dependence); in patients with mania, depression, or schizophrenia (along with careful psychiatric monitoring); in patients receiving concomitant therapy with sedatives, hypnotics, or other psychoactive drugs; and in pregnant patients, nursing mothers, or pediatric patients.

Solvay Pharmaceuticals, Inc. and Nektar Therapeutics entered into a collaboration in 2002 to develop the metered dose inhaler (MDI) for dronabinol (synthetic delta-9-tetrahydrocannabinol) to be used for multiple indications. Nektar developed the formulation, and is responsible for the clinical and commercial manufacturing of the drug formulation and inhaler combination. Solvay Pharmaceuticals, Inc. is responsible for the clinical development and worldwide commercialization of the system.

Solvay Pharmaceuticals, Inc. ( of Marietta, Ga. (USA) is a research-driven pharmaceutical company that seeks to fulfill unmet medical needs in the therapeutic areas of cardiology, gastroenterology, mental health, women's health and a select group of specialized markets including men's health. It is a part of the global Solvay Pharmaceuticals organization whose core activities consist of discovering, developing and manufacturing medicines for human use. Solvay Pharmaceuticals, Inc. is a subsidiary corporation of the worldwide Solvay Group of chemical and pharmaceutical companies headquartered in Brussels, Belgium.

Nektar Therapeutics ( provides industry-leading drug delivery technologies, expertise, and manufacturing to enable the development of high-value, differentiated therapeutics. Nektar's advanced drug delivery capabilities are designed to enable the Company's biotechnology and pharmaceutical partners to solve drug development challenges and realize the full potential of their therapeutics, from developing new molecular entities to managing the life cycles of established products.

1. Martin BR, Wiley JL. Mechanism of action of cannabinoids: how it may lead to treatment of cachexia, emesis, and pain. J Support Oncol. 2004;2:305-316.