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Synephrine pharmacokinetics and cardiovascular changes after ingestion of citrus aurantium dietary supplements
Author(s) -
Haller C. A.,
Duan M.,
Jacob P.,
Benowitz N. L.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.11.022
Subject(s) - cmax , caffeine , placebo , crossover study , chemistry , pharmacokinetics , ingestion , pharmacology , washout , blood pressure , heart rate , zoology , stimulant , medicine , endocrinology , biochemistry , alternative medicine , pathology , biology
Background Ephedra‐free weight loss dietary supplements (DS) containing Citrus aurantium (CA), a botanical source of the adrenergic amines synephrine (SYN) and octopamine, have rapidly replaced banned ephedra products, but have not been adequately studied. These DS may have some of the health risks associated with ephedra. We present novel data on CA PK/PD in humans. Methods In a randomized, double blind, placebo‐controlled crossover study, 10 healthy adults took 1 oral dose of CA alone (Advantra Z®, (ADV) with 45 mg SYN), and a multi‐component DS (Xenadrine EFX® (XEN) with 5.5 mg SYN), with a 1‐week washout between treatments. Plasma drug levels were measured over 12 hours by LC‐MS/MS. Results XEN but not ADV increased systolic and diastolic BP with peak changes over placebo at 2 hrs of 9.6 ± 6.2 mm Hg systolic (p=0.047), and 9.1 ± 7.8 mm Hg diastolic (p=0.002). Heart rate was increased at 6 hrs (16.7 bpm with XEN, p=0.011; 11.4 bpm with ADV, p=0.031). SYN C max was 2.8 ng/ml with ADV and 0.35 ng/ml with XEN. Caffeine C max was 5.1 mcg/ml with XEN. Plasma levels of octopamine were negligible. Dose‐adjusted SYN PK were similar between treatments with t max = 90 min, t 1/2 = 3.0 hrs, V/F= 16347 L, and CL/F= 88.9 L/min for XEN. Conclusions Ephedra‐free weight loss DS have significant cardiovascular stimulant actions. These pressor effects are not likely caused by CA, since a 8‐fold higher dose of synephrine (ADV) had no effect on blood pressure, but may be attributable to caffeine and other stimulants in the DS. Clinical Pharmacology & Therapeutics (2005) 77 , P5–P5; doi: 10.1016/j.clpt.2004.11.022