Promethazine (Phenergan) is a widely used antihistaminic, antiemetic, and sedative drug. Zamen et al. (1986) undertook a study to determine the dose proportionality of promethazine from the tablet dosage form. Following the administration of one tablet containing either 25 or 50 mg of promethazine, plasma concentrations were measured (Table P2.2). Plot the data and, using the plot, determine the following:
a. The elimination half-life (t1/2) for each dose.
b. The elimination rate constant (K) for each dose.
c. The absorption half-life (t1/2abs) for each dose.
d. The absorption rate constant (K) for each dose.
e. The observed and computed peak time (tmax) for each dose.
f. The observed and computed peak plasma concentrations, (Cp)max, for each dose.
g. The y-axis intercept for each dose.
h. The apparent volume of distribution (V).
i. The fraction of drug absorbed (F).
j. The characteristics of a plot on rectilinear paper of peak time (tmax) against the administered dose, then make an important observation.
Table P2.2
Time (h)
Mean plasma concentrations (ng mL-1)
25mg tablet (lot 1821448)
50mg tablet (lot 1821148)
0.5 0.12 0.26
1.0 0.45 0.75
1.5 2.20 3.62
2.0 1.76 3.05
3.0 5.38 6.65
4.0 4.26 4.15
6.0 6.80 6.91
8.0 4.42 3.42
10.0 6.32 6.54
12.0 2.90 2.43
24.0 4.85 4.25
- 2.00
- 3.60
- 1.53
- 2.72
- 1.27
- 2.30
- 1.35
- 0.67
- 0.94
- 2.07
- 1.64
Mean SD of 15 determinations. Products made by Wyeth Laboratory.
