Pharmacodynamics and pharmacokinetics of single nasal (5 mg and 10 mg) andoral (50 mg) doses of ephedrine in healthy subjects

Objective: To determine the cardiovascular, subjective effects and potentia l of abuse liability of single dose (-) ephedrine (E) administered orally ( 50 mg) or intranasally (10 mg and 5 mg). Methods: Sixteen healthy Caucasian men with no history of drug/alcohol/nico tine abuse or dependence received intranasal single doses of E 5 mg, 10 mg and oral doses of 50 mg and placebo in a double-blind, double-dummy, crosso ver study. Dependent measures included assessment of subjective feelings by Addiction Research Centre Inventory (ARCI), Profile of Mood States (POMS), visual analogue scales (VAS); "drug liking", "any drug effect", subjective quality of sleep and blood pressure and heart rate. Plasma E concentration s were also determined. Results: (-) E increased supine systolic, diastolic blood pressure (P < 0.0 1). Changes in supine systolic blood pressure (areas under the 8 h of the e xperimental sessions) were -59 +/- 47 mmHg(.)h with placebo, -59 +/- 57 mmH g(.)h with E 5 mg by the nasal route, - 18 +/- 48 mmHg(.)h with E 10 mg by the nasal route and 13 +/- 58 mmHg(.)h with E 50 mg by the oral route (P < 0.001). (-) E-induced orthostatic hypotension (P <0.01) (maximal systolic b lood pressure drop: E 50 mg 14 +/- 10 mmHg, P < 0.03; E 10mg 11 +/- 6mmHg, P=0.08 compared with placebo) and resulted in decreased tiredness (placebo -2 +/- 39mm(.)h, E 5mg -17 +/- 39mm(.)h, E 10 mg -30 +/- 42 mm(.)h, E 50 mg -24 +/- 35 mm(.)h; P < 0.03). E did not modify ARCI subscales - in particu lar the "amphetamine" subscale - but showed a tendency for drug liking (P = 0.09). On the "any drug effect" questionnaire, subjects could identify dru g effect (P = 0.007). Maximal plasma E concentration (Cma.,) and areas unde r the curves for up to 8 h were proportional to the doses. Elimination half -life was approximately 6 h. A clockwise hysteresis was observed for systol ic blood pressure in all but one subject with E 50 mg by the oral route. Conclusion: E even at low doses and by the nasal route can decrease tiredne ss in healthy persons;, this is accompanied by a substantial increase in bl ood pressure and orthostatic hypotension exposing individuals in case of in tensive physical exercise to cardiovascular risks. No clear evidence of abu se liability in healthy drug naive subjects was observed.