Aerosol delivery of ergotamine tartrate via a breath-synchronized plume-control inhaler in humans.
OBJECTIVE
To compare systemic delivery of ergotamine tartrate (ET) via a breath-synchronized, plume-control inhaler (BSPCI) (Tempo ET) with a sublingual ergot preparation and a commercial inhaler.


METHODS
Study 1 determined plasma ET concentrations in seven healthy subjects after administration of ET by a 2 mg tablet (Lingraine) and a BSPCI delivering 258 microg of ET. Study 2 determined plasma ET concentrations in 16 healthy subjects after administration via an ET metered dose inhaler (ME) (Medihaler) delivering 2052 microg of ET and a BSPCI delivering 129 microg of ET. Gamma scintigraphy with (99m)Tc validation was used to quantify lung deposition.


RESULTS
For both studies, ET C(max) was higher with the BSPCI (study 1: sublingual ET 134 pg/mL at 37 min; BSPCI 3743 pg/mL at 3 min; study 2: metered-dose inhaler 1109 pg/mL at 4 min; BSPCI 1210 pg/mL at 2.5 min). Mean dose normalized AUC was several-fold higher with the BSPCI compared with sublingual ET and ME dosing. Lung deposition of ET with the BSPCI was 33.5, 8.9, 11.4, and 13.2% for whole, central, intermediate, and peripheral lung, respectively, with a 1.5 peripheral : central ratio.


CONCLUSIONS
Based on these open-label studies, the BSPCI allows rapid delivery of potentially therapeutic plasma concentrations of ET at approximately 1/15th the dose of comparators.
Armer
T A
TA
MAP Pharmaceuticals, Mountain View, CA 94043, USA.
Shrewsbury
S B
SB
Newman
S P
SP
Pitcairn
G
G
Ramadan
N
N
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000336:Aerosols; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004878:Ergotamine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D013607:Tablets; D014018:Tissue Distribution
D000336:Aerosols; D018712:Analgesics, Non-Narcotic; D013607:Tablets; D004878:Ergotamine