topotecan pharmacokinetics: gender-related differences

Inpharma 1266 - 2 Dec 2000 Topotecan pharmacokinetics: gender-related differences There appear to be significant gender-related differences in the pharmacokinetics of topotecan in patients with solid tumours, report researchers from The Netherlands. In this study, 54 evaluable patients (36 men) with solid tumours received oral topotecan [‘Hycamtin’] in combination with IV cisplatin (oral phase), and 38 evaluable patients (19 men) received IV topotecan (IV phase). * The topotecan lactone:total topotecan AUC ratio was significantly higher in women, compared with men, during the oral phase (41.7 vs 37.1%) and the IV phase (34.1 vs 29.6%). The apparent clearance of topotecan lactone was significantly slower in women, compared with men, during the oral phase (163 vs 237 L/h) but not during the IV phase (59.9 vs 73.9 L/h). Haematocrit significant predictor of clearance Haematocrit values were significantly lower in women, compared with men, in both the oral and IV phases. The researchers also found that ‘hematocrit was a significant predictor for the apparent clearance of topotecan lactone’. The role of haematocrit as a contributing factor to the observed gender differences in topotecan pharmacokinetics was further confirmed in in vitro studies. Thus, the researchers conclude that ‘topotecan is subject to significant gender-dependent differences in pharmacokinetic behavior that result from a physiologic difference in hematocrit values between males and females’. * In the oral phase, patients received topotecan 0.75–2.3 mg/m 2 /day for 5 days every 3 weeks, in combination with IV cisplatin 75 mg/m 2 ; some patients received IV cisplatin 50 mg/m 2 on day 1 of each cycle followed by topotecan 1.5 or 1.75 mg/m 2 /day for 5 days. In the IV phase, patients received a 21-day continuous infusion of IV topotecan 0.5 or 0.6 mg/m 2 /day every 28 days. Loos WJ, et al. Gender-dependent pharmacokinetics of topotecan in adult patients. Anti-Cancer Drugs 11: 673-680, Oct 2000 800853502 1 Inpharma 2 Dec 2000 No. 1266 1173-8324/10/1266-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved

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Inpharma 1266 - 2 Dec 2000

Topotecan pharmacokinetics:gender-related differences

There appear to be significant gender-relateddifferences in the pharmacokinetics of topotecan inpatients with solid tumours, report researchers from TheNetherlands.

In this study, 54 evaluable patients (36 men) withsolid tumours received oral topotecan [‘Hycamtin’] incombination with IV cisplatin (oral phase), and 38evaluable patients (19 men) received IV topotecan (IVphase).*

The topotecan lactone:total topotecan AUC ratio wassignificantly higher in women, compared with men,during the oral phase (41.7 vs 37.1%) and the IV phase(34.1 vs 29.6%). The apparent clearance of topotecanlactone was significantly slower in women, comparedwith men, during the oral phase (163 vs 237 L/h) but notduring the IV phase (59.9 vs 73.9 L/h).

Haematocrit significant predictor ofclearance

Haematocrit values were significantly lower inwomen, compared with men, in both the oral and IVphases. The researchers also found that ‘hematocrit wasa significant predictor for the apparent clearance oftopotecan lactone’. The role of haematocrit as acontributing factor to the observed gender differences intopotecan pharmacokinetics was further confirmed in invitro studies.

Thus, the researchers conclude that ‘topotecan issubject to significant gender-dependent differences inpharmacokinetic behavior that result from a physiologicdifference in hematocrit values between males andfemales’.* In the oral phase, patients received topotecan 0.75–2.3 mg/m2/dayfor 5 days every 3 weeks, in combination with IV cisplatin 75 mg/m2;some patients received IV cisplatin 50 mg/m2 on day 1 of each cyclefollowed by topotecan 1.5 or 1.75 mg/m2/day for 5 days. In the IVphase, patients received a 21-day continuous infusion of IV topotecan0.5 or 0.6 mg/m2/day every 28 days.

Loos WJ, et al. Gender-dependent pharmacokinetics of topotecan in adult patients.Anti-Cancer Drugs 11: 673-680, Oct 2000 800853502

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