Ephedrine hydrochloride

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Scientifically valid publication (human volunteer study)

Data source

Reference

Reference Type:

publication

Title:

THE PHARMACOKINETICS OF EPHEDRINE AFTER ORAL DOSAGE IN ASTHMATICS RECEIVING ACUTE AND CHRONIC TREATMENT

Author:

Pickup M.E.

Year:

1976

Bibliographic source:

Br.J.clin.Pharmac. (1976), 3, 123-134

Materials and methods

Type of study / information:

clinical trial

Endpoint addressed:

basic toxicokinetics

Test guideline

Qualifier:

no guideline followed

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ephedrine hydrochloride

EC Number:

200-074-6

EC Name:

Ephedrine hydrochloride

Cas Number:

50-98-6

Molecular formula:

C10H15NO.ClH

IUPAC Name:

2-(methylamino)-1-phenylpropan-1-ol hydrochloride

Constituent 2

Reference substance name:

(-)- Ephedrine hydrochloride

IUPAC Name:

(-)- Ephedrine hydrochloride

Details on test material:

- Name of test material: (-)-Ephedrine hydrochloride

Method

Details on exposure:

Ten hospital outpatients, ranging in age from 25-51 years and receiving bronchodilator therapy (normally salbutamol) until the day preceding the investigation, volunteered for the studies.


TYPE OF EXPOSURE:

Oral as solution or in tablet form

TYPE OF EXPOSURE MEASUREMENT:

Plasma and urine collections

Ephedrine plasma Ievels were monitored; blood samples were drawn into Iithium heparin tubes at approximately the following times for each study: 0 (i.e. the blank determination), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4 .0, 5.0, 6.0, 7.0, 8.0 hours. Sufficient blood was taken to allow separation of the plasma into 2 x 3 mL portions. For Studies A1 and B3, 36 h urine samples were collected.


EXPOSURE LEVELS:

20-22 mg were given before and after 2 weeks' treatment with ephedrine hydrochloride, 10-11 mg were given three times a day


EXPOSURE PERIOD / DESCRIPTION OF EXPOSURE GROUPS :

a)
An oral dose of (-)-ephedrine hydrochloride (22 mg) was given in solution before (Study A1) and after (Study A2) 2 weeks' treatment with ephedrine hydrochloride ( 11 mg three times a day), and

(b)
Two tablets 4332 were given before (Study B3) and after (Study B4) 2 weeks' treatment with one tablet three times a day.

A period of at least 2 weeks was allowed between (a) and (b) during which no ephedrine medication was prescribed.

Results and discussion

Results:

Toxicokinetic parameters

#1

Half-life 1st: 6.75 h (mean)


#2

Half-life 1st: 6.69 h (mean)


#3

Half-life 1st: 5.74 h (mean)


#4

Half-life 1st: 5.22 h (mean)

Any other information on results incl. tables

(i) Peak plasma Ievels (Cm):

Computer estimated peak plasma Ievels ranged from 52.7-138.8 (mean 79.4 ng mL-1) following ephedrine dosage (Study A1). The times at which the peak occurred [ t (Cm)] was an average 1.81 h after drug administration. In Study A2, peak plasma Ievels ranged from 66-118.6 (mean 87.4 ng mL-1 ) occurring 1.86 h after administration. Similarly, for the compound tablet studies, a range of 44.7-11 1.1 (mean 73.9 ng mL -1) was recorded after 1.69 h for study B3, and a range of 65.7-107.3 (mean 77.2 ng mL -1 ) after 1.47 h for study B4.

(ii) Biological availability (f) :

The availability of ephedrine from the tablet form, assuming each tablet contains ephedrine HCI (11 mg), was calculated as 0.88.

(iii)

Plasma half-life (t 1/2): These ranged from 4.48-11.48 (mean 6.75 h) for Study A1; 3.09-9.9 (mean 6.69 h) for study A2 ; 3.54-10.45 (mean 5.74 h) for study B3 and 3.29-8.56 (mean 5.22 h) for study B4.

(iv) Plasma clearance (V pl):

The mean clearance calculated in turn for each of the studies A 1, A2, B3 and B4 was 23.3, 25.4, 28.7 and 30 L h -1, respectively.

(v) Apparent volume of distribution (Vd):

The mean volume of distribution for each of the studies was found to be 215.6, 230, 213.7 and 203.4 L, respectively.

(vi) Statistical analysis:

Results of paired t-tests indicated no significant (P > 0.05) difference in half-life, plasma clearance, rate constant and time of peak plasma Ievel comparing data from:

(a) Acute and chronic ephedrine studies

(b) Acute ephedrine and acute compound tablet studies

(c) Acute and chronic compound tablet studies

There was no significant correlation between the pH of 36 h urine and the corresponding half-life in each subject. A significant correlation between the volume of distribution and the half-life could only be demonstrated in two patients. A significant correlation was obtained between body weight and volume of distribution in the acute studies A1 and B3 (P< 0.01 and < 0.05 respectively), and between body weight and the peak plasma level, Cm, in Study A1 only (P < 0.05).