Table 2.
Mean pharmacokinetic parameter values of dextromethorphan (DEX) and dextrorphan (DOR) according to the best fit models 9 and 7 (Table 1).*
| Treatment groups | Total clearance (l h−1) | Intrinsic metabolic clearance (l h−1) | Non-metabolic clearance (l h−1) | V (l) | ka(h−1) | tlag(h) | FH(%) | [I]/Ki | t1/2[1] (h) | t1/2[2] (h) | k(DOR) (h−1) | [V(DOR)/ F(DOR)](l) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DEX (30 mg) | 75 | 523 | 3 | 961 | 2.6 | 0.8 | 20 | NA | 3.1 | 17 | 0.51 | 3776 |
| (13) | (257) | (0) | (167) | (0.9) | (0.1) | (15) | (0.3) | (4) | (0.21) | (1382) | ||
| [39–85] | [59–910] | [585–1292] | [0.8–3.9] | [0.5–1.2] | [9–60] | [2.3–3.7] | [10–24] | [0.21–1.07] | [1222–6441] | |||
| DEX (60 mg) | 78a | 788a | 3 | As above | 2.0a | 0.6ab | 16a | NA | 3.1 | 16 | As above | As above |
| (12) | (528) | (0) | (0.9) | (0.1) | (14) | (0.3) | (4) | |||||
| [43–88] | [73–1536] | [0.5–3.4] | [0.5–1.0] | [6–55] | [2.2–3.8] | [9–26] | ||||||
| DEX (30 mg) | 20c | 27c | 3 | As above | 1.1c | 0.7 | 78c | 19 | 3.6c | 58c | 0.34c | As above |
| + Quinidine | (9) | (14) | (0) | (0.7) | (0.3) | (10) | (2) | (0.5) | (38) | (0.14) | ||
| (50 mg) | [3–35] | [3–56] | [0.3–2.4] | [0.3–1.7] | [62–97] | [13–23] | [2.7–5.2] | [24–145] | [0.11–0.63] |
*
The numbers in parentheses indicate SD and those in square brackets are the range for each parameter. For a full description of parameters see Appendix. NA, Not applicable.
a
Significantly different from 30-mg arm (P < 0.02);
b
significantly different from quinidine arm (P < 0.05);
c
significantly different from corresponding parameter value in absence of quinidine (P < 0.001).