Nederlands Platform voor Farmaceutisch Onderzoek

Het Nederlands Platform voor Farmaceutisch Onderzoek (NPFO) presenteert onderzoek in de farmaceutische wetenschappen, zoals medicatieveiligheid, patiëntenzorg, formulering, (bio)analyse, (klinische) farmacologie en casuïstiek.

Praktijkonderzoek naar effect van depressie op therapietrouw

Jacqueline Hugtenburg

Rubriek: Referaat
Identificatie: 2016;1:e1602
Datum: 18 januari 2016

Dankbetuiging

Rubriek: Redactionele mededeling
Identificatie: 2016;1:e1601
Datum: 18 januari 2016

Speeksel als matrix voor meting van pyrazinamide bij farmacokinetisch onderzoek en therapeutic drug monitoring

C.A.W. Heijens a*, H.H. Semvua b, C.M. Mtabho b, M.J. Teulen c, A.P. Colbers c, P.M.G. Filius a, D.M. Burger c, G.S. Kibiki b en R.E. Aarnoutse c

Lees abstract

Saliva as a matrix for the measurement of pyrazinamide in pharmacokinetic studies or therapeutic drug monitoring

OBJECTIVE

To describe the pharmacokinetics of pyrazinamide in saliva and to assess whether saliva can be a matrix for pharmacokinetic studies and therapeutic drug monitoring (TDM).

DESIGN AND METHODS

Intensive pharmacokinetic sampling for both plasma and saliva took place during 24 h in 15 adult tuberculosis patients in Moshi, Tanzania. Pharmacokinetic parameters for both matrices were derived from the measured saliva and total (protein-bound plus unbound) plasma concentrations of pyrazinamide. The reciprocal saliva/plasma concentration ratio was used to estimate plasma concentrations based on the measured salivary concentrations. The predictive performance of these estimations was assessed by the jackknife method.

RESULTS

Geometric means of AUC0-24 and Cmax of pyrazinamide in saliva were 61% and 78%, respectively, of the corresponding values in plasma. tmax in saliva was similar to that in plasma. Salivary concentrations and total plasma concentrations (n = 133) were strongly correlated (Spearman’s rho = 0.909; P < 0.001). The mean plasma/saliva concentration ratio was 0.637 (CI95 0.600-0.673). The ratio was dependent on the sampling time. It was highest in the absorption phase and decreased afterwards. Bias and imprecision of the prediction of total pyrazinamide plasma concentrations based on salivary concentrations were 5.5% and 24.7%, respectively. Using samples in a time window of t = 2-8 h post dose, bias was 13.5% and imprecision was 21.4%.

CONCLUSION

The exposure to pyrazinamide in saliva is relatively high, but less than the exposure in plasma. The saliva/plasma concentration ratio was time-dependent, contributing to an insufficient predictive performance (imprecision > 20%). Based on this study saliva measurements of pyrazinamide can only be used for a semiquantitative assessment of pyrazinamide plasma concentrations.

Rubriek: Korte bijdrage
Identificatie: 2016;1:a1601
Datum: 18 januari 2016

Contact

Redacteur / secretaris
Arjan Polderman

(070) 373 73 14 npfo@npfo.nl