The kinetics of salivary elimination of cyclophosphamide in man.

Abstract

1 The concentrations of cyclophosphamide in plasma and saliva were determined in seven patients following administration of single doses of cyclophosphamide during chemotherapy for lymphoma. 2 The saliva/plasma ratio was 0.77 +/‐ 0.24 (s.d.) and showed no time‐ dependence being rapidly established following intravenous and oral administration. 3 The T 1/2 of cyclophosphamide (8.38 +/‐ 2.25 h) determined from salivary measurements was not significantly different from that in plasma (8.24 +/‐ 2.60 h). It was not possible to estimate the apparent volume of distribution or total body clearance utilizing the salivary cyclophosphamide concentration without appropriate correction for the saliva/plasma concentration ratio. 4 The binding to the plasma protein of normal plasma of cyclophosphamide was 13.4 +/‐ 5.3%. The Scatchard plot for binding to bovine serum albumin indicates only weak binding to non‐specific sites. 5 Salivary cyclophosphamide therefore indicates the concentration of the unbound fraction of plasma cyclophosphamide.

Urinary excretion and pharmacokinetics of acrolein and its parent drug cyclophosphamide in bone marrow transplant patients

“…It is only recently that more interest has been placed on the pharmacokinetics of CP in high-dose therapy. 13,14 While the ␤-phase half-life (t 1/2␤ ) of CP obtained in this study is consistent with values reported previously, [15][16][17][18][19] the value of the ␤-phase volume of distribution (V t ) in this study was somewhat larger than those previously reported for the volume of distribution in humans, 20 which resulted in a markedly larger total clearance (CL) of CP as compared to that reported by other investigators. 16,19,21 It should be noted that when a similarly higher dose of CP was used, the volume of distribution at steady state (V ss ) (ie, 30.20 l) 12 was somewhat close to the value of V ss calculated in this study (ie 39.23 l).…”

Suggestions for Protecting Breast Cancer Patients Receiving Outpatient Chemotherapy and Their Families Against the Exposure Risk from Salivary Cyclophosphamide

“…CPA in saliva was 13.6-79.0 (33.1 ± 13.2) mg/mL immediately after the chemotherapy, and then exponentially decreased with the passage of time (half-life of 6.62 ± 1.24 h, elimination rate constant of 0.171) (Figure 1). These values were slightly lower than that determined from saliva in male patients undergoing chemotherapy (half-life of 8.38 ± 2.25 h, elimination rate constant of 0.275) [8]. These results suggest that there are no sex differences in the elimination of CPA.…”

“…including CPA) and had Performance Status (PS)of 0 or 1 (irrespective of age) [8]. The patients were asked to keep saliva for 3 days after outpatient chemotherapy.…”

Lack of correlation between methotrexate concentrations in serum, saliva and sweat after 24 h methotrexate infusions.

“…Efforts have been made to investigate, if saliva could be used as a noninvasive method for monitoring therapeutic drug concentrations (Danhof & Breimer, 1978). Concerning cytotoxic drugs such studies have been few including only a small number of patients (Juma et al, 1979;Patterson et al, 1981;Ritschel et al, 1981;Slavik et al, 1983;Steele et al, 1979). In the two hitherto published reports on MTX excretion in saliva there has been no general agreement as to the correlation between serum MTX and saliva Correspondence: Dr H. Schr0der, Department of Pediatrics, Aarhus Kommunehospital, DK 8000 Aarhus C, Denmark MTX concentrations (Patterson et al, 1981;Steele et al, 1979).…”