| In vitro model |
Results |
Talinolol Detection |
Ref. |
| Caco-2 cells |
S-(-)-talinolol: R(B-A/A-B) ≈ 9.6; R-(+)-talinolol: R(B-A/A-B) ≈ 8.7
After addition of verapamil (0.5 mM):
S-(-)-talinolol: R(B-A/A-B) ≈ 1.41; R-(+)-talinolol: R(B-A/A-B) ≈ 1.39 |
HPLC |
[180] |
| |
S-(-)-talinolol: R(B-A/A-B) ≈ 39.6
R-(+)-talinolol: R(B-A/A-B) ≈ 30.5
After addition of verapamil (0.5 mM):
S-(-)-talinolol: Papp (A-B) enhanced from 0.16x10-6 to 1.81x10-6cm/s
R-(-)-talinolol: Papp (A-B) enhanced from 0.19x10-6 to 1.8110-6cm/s
After addition of GFJ (50%):
S-(-)-talinolol: Papp (A-B) enhanced from 0.16x10-6to 0.61x10-6cm/s
R-(-)-talinolol: Papp (A-B) enhanced from 0.19x10-6to 0.71x10-6cm/s |
HPLC-UV |
[181] |
| |
Racemic talinolol: R(B-A/A-B) ≈ 7.4
After addition of verapamil (0.5 mM): R(B-A/A-B) ≈ 3.0 |
HPLC-FL |
[182] |
| |
R(B-A/A-B) of talinolol obtained among 10 different laboratories: 1.03 – 25.6 |
- |
[183] |
| MDR1-Caco2 |
S-(-)-talinolol: R(B-A/A-B) ≈ 69.0
R-(+)-talinolol: R(B-A/A-B) ≈ 55.7 |
HPLC-UV |
[184] |
| L-MDR1 |
Racemic talinolol: R(B-A/A-B): 2.71±0.02
After addition of cyclosporin A: R(B-A/A-B): 0.66±0.02 |
LC-MS/MS |
[129] |
| Rat intestine mounted in Ussing chamber |
Papp (A-B): 6.83±0.26; Papp (B-A): 25.3±2.30; R(B-A/A-B): 3.70±0.24
After addition of verapamil (200 µM)
Papp (A-B): 18.08±1.18; Papp (B-A): 5.46±0.99; R(B-A/A-B): 0.30±0.04 |
HPLC-UV |
[185] |
| Animal Studies |
Brief Procedure |
Results |
Talinolol Detection |
Ref. |
| Rat |
In situ perfusion in duodenum, jejunum and colon segments of rat intestine |
No differences between distinct segments;
Pre-treatment with rifampin increased talinolol Papp from:
2.44 x10-4 to 1.82x10-4 cm/s in duodenum; 2.50 x10-4 to 1.51 x10-4 cm/s in jejunum; 2.46 x10-4 to 1.98 x10-4 cm/s in colon. |
HPLC-UV |
[186] |
| NMR1 mice |
In situ perfusion |
Verapamil enhanced 5-fold the Papp of talinolol. |
HPLC |
[187] |
| Abcb1a/b (-/-) mice |
In situ perfusion |
In relation to wild type animals, talinolol Papp enhanced 7-fold. |
| Sprague-Dawley Rats |
Oral administration of racemic talinolol (10 mg/Kg ) and GFJ |
S-(-)-talinolol:
Cmax increased from 77.5 to 163.6 ng/mL
AUC increased from 19.3 to 29.9 µg/mL.min
CL/F decreased from 382 to 182 mL/min
R-(-)-talinolol:
Cmax increased 79.5 to 163.0 ng/mL
AUC increased from 22.2 to 30.1 µg/mL.min
CL/F decreased from 242 to 192 mL/min |
HPLC-UV |
[181] |
| Studies in humans |
Brief description |
Results |
Talinolol Detection |
Ref. |
| Mechanistic clinical studies |
Triple lumen tubing technique (intestinal perfusion method)
IV infusion of talinolol |
Intra-luminal talinolol concentrations were 5.5-fold higher than those in serum. |
HPLC |
[174] |
Triple lumen tubing technique (intestinal perfusion method)
IV infusion of talinolol and R-verapamil |
Intestinal secretion rate of talinolol diminished 44-71% after administration of R-verapamil. |
HPLC |
[188] |
| Clinical Studies |
Controlled and randomized clinical study in 8 healthy volunteers administered with rifampin (600 mg id, for 9 days) and then with talinolol |
After oral administration of talinolol
AUC diminished by 35%
Cmax decreased by 38%
Oral bioavailability decreased by 20%.
After IV administration of talinolol
AUC diminished by 21%
Cmax decreased by 20% |
HPLC-FL |
[177] |
| Controlled and randomized clinical study in 9 healthy volunteers administered with SJW (900 mg id, for 12 days) and then with talinolol |
After oral administration of talinolol
Oral bioavailability reduced by 25%.
AUC decreased by 31%
Oral clearance increased by 93%
After IV administration of talinolol
Nonrenal clearance enhanced by 35% |
HPLC |
[189] |
