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Do topotecan concentrations in saliva reflect plasma concentrations?

Department of Medical Oncology, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam, The Netherlands, Department of Pharmacy, Slotervaart Hospital, Amsterdam, The Netherlands

H. Rosing, MSc

Department of Pharmacy, Slotervaart Hospital, Amsterdam, The Netherlands

WW ten Bokkel Huinink, MD

Department of Medical Oncology, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam, The Netherlands

Raa Maes, PhD

Department of Pharmaceutical Analysis and Toxicology, Faculty of Pharmacy, State University of Utrecht, Utrecht, The Netherlands

JH Beijnen, PhD

Department of Medical Oncology, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam, The Netherlands, Department of Pharmacy, Slotervaart Hospital, Amsterdam, The Netherlands, Department of Pharmaceutical Analysis and Toxicology, Faculty of Pharmacy, State University of Utrecht, Utrecht, The Netherlands

Purpose. There is an increasing interest to use saliva as biological fluid for drug monitoring as it reflects adequately, in some cases, drug concentrations in plasma. A great advantage is that it can be obtained conveniently by a noninvasive method. We describe our experience with respect to the practical use of saliva for pharmacokinetic monitoring of the novel anticancer agent topotecan.

Patients and Methods. Eighty-one saliva sam ples and corresponding plasma samples were ob tained 2 hours after the end of infusion from 15 patients with either ovarian cancer or small cell lung cancer, receiving 1.5 mg/m ² per day topotecan for 5 consecutive days every 3 weeks. Saliva was obtained by a citric-acid containing dental cotton roll which stimulated the saliva flow.

Results. The plasma topotecan concentrations varied between 3.67 and 24.4 ng/mL, with an intrapa tient (day-to-day) variation of only 9.8%, and an inter patient variation of 27.2%. The saliva concentrations varied between 5.34 and 74.2 ng/mL, with an intrapa tient variation of 25.3%, and an interpatient variation of 53.5%. The mean plasma/saliva topotecan ratio was 0.66 (range 0.21 to 1.58) and was both patient dependent and dependent on the sampling time. The day-to-day variation of the plasma/saliva concentra tion ratio in this daily times five schedule was 27.6%, and the interpatient variation was 45.5%. The saliva concentrations of topotecan were not related to the occurrence of mucositis, which was noted in some patients.

Conclusion. Based on the large variability in the plasma/saliva ratios, we conclude that in our investi gational setting saliva is not a reliable matrix for topotecan analysis and that plasma sampling is to be preferred.

Key Words: Pharmacokinetics • saliva • topote can.

Journal of Oncology Pharmacy Practice, Vol. 1, No. 1, 41-45 (1995)
DOI: 10.1177/107815529500100105


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