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The pharmacokinetics of midazolam and 1-hydroxymethylmidazolam were investigated following oral administration of 7.5, 15 and 30 mg doses of midazolam in solution to 12 healthy subjects. Compared to the 7.5 mg dose, the Cmax and AUC parameters of both midazolam and 1-hydroxymethylmidazolam increased proportionally after the 15 mg dose and more than proportionally after the 30 mg dose. The t1/2 for midazolam remained relatively constant between the 7.5 and 15 mg doses whereas it increased slightly but significantly after the 30 mg dose. These data indicated that the pharmacokinetics of midazolam and 1-hydroxymethylmidazolam were linear between the 7.5 and 15 mg oral dose range. However, after the 30 mg dose, the systemic availability of midazolam and the AUC for 1-hydroxymethylmidazolam appeared to be greater than that anticipated from the lower doses, possibly due to saturation of midazolam first-pass metabolism. This is not expected to have any clinical significance under the conditions of therapeutic use.
L D Bornemann, and
B H Min, and
T Crews, and
M M Rees, and
H P Blumenthal, and
W A Colburn, and
I H Patel
March 2023,
Xenobiotica; the fate of foreign compounds in biological systems,
L D Bornemann, and
B H Min, and
T Crews, and
M M Rees, and
H P Blumenthal, and
W A Colburn, and
I H Patel
January 1983,
Pharmacology & therapeutics,
L D Bornemann, and
B H Min, and
T Crews, and
M M Rees, and
H P Blumenthal, and
W A Colburn, and
I H Patel
January 1986,
Journal of clinical pharmacology,
L D Bornemann, and
B H Min, and
T Crews, and
M M Rees, and
H P Blumenthal, and
W A Colburn, and
I H Patel
December 1993,
Critical care medicine,
L D Bornemann, and
B H Min, and
T Crews, and
M M Rees, and
H P Blumenthal, and
W A Colburn, and
I H Patel
November 1977,
European journal of clinical pharmacology,
L D Bornemann, and
B H Min, and
T Crews, and
M M Rees, and
H P Blumenthal, and
W A Colburn, and
I H Patel
January 1986,
European journal of clinical pharmacology,
L D Bornemann, and
B H Min, and
T Crews, and
M M Rees, and
H P Blumenthal, and
W A Colburn, and
I H Patel
May 1987,
British journal of clinical pharmacology,
L D Bornemann, and
B H Min, and
T Crews, and
M M Rees, and
H P Blumenthal, and
W A Colburn, and
I H Patel
November 1997,
Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie : AINS,
L D Bornemann, and
B H Min, and
T Crews, and
M M Rees, and
H P Blumenthal, and
W A Colburn, and
I H Patel
January 1981,
Cancer chemotherapy and pharmacology,
L D Bornemann, and
B H Min, and
T Crews, and
M M Rees, and
H P Blumenthal, and
W A Colburn, and
I H Patel
May 1996,
Biopharmaceutics & drug disposition,
