Salivary concentrations of hexamethylene bisacetamide (HMBA) in patients receiving 5-day continuous infusions.
Salivary and plasma concentrations of hexamethylene bisacetamide (HMBA) were studied to determine (1) how the concentrations of HMBA achieved in saliva compared with those required to induce differentiation in vitro, and (2) whether saliva might substitute for plasma as a biologic fluid on which to base dosage adjustment. Plasma and expectorated saliva were collected concomitantly from 16 patients receiving 5-day continuous infusions of HMBA. The concentrations of HMBA in each fluid were determined by gas chromatography. The patients displayed a range of periodontal disease from gingivitis to complete edentia, but periodontal disease status did not appear to influence the salivary behavior of HMBA, which mirrored that of the drug in plasma, with concentrations of HMBA increasing in both fluids during the first 12-16 h of infusion. Between 24 and 120 h, HMBA concentrations in saliva and plasma remained constant. In some patients, salivary HMBA concentrations lagged behind those in plasma during the first 6-8 h of infusion, but after that the salivary HMBA concentrations approximated those in the plasma. Salivary concentrations of HMBA between 0.96 and 2.56 mM were associated with nontoxic plasma concentrations of HMBA. Therefore, in patients with restricted venous access, saliva might be a suitable substitute for plasma if adaptive control-dosing schemes for HMBA are employed. Moreover, the concentrations of HMBA in saliva bathing the oral cavity are quantitatively comparable to those required for induction of cell differentiation in vitro.
Conley
B A
BA
Division of Developmental Therapeutics, University of Maryland Cancer Center, Baltimore 21201.
Egorin
M J
MJ
Zuhowski
E G
EG
Sinibaldi
V J
VJ
Peterson
D E
DE
D000081:Acetamides / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007262:Infusions, Intravenous; D012463:Saliva / Q000032:analysis*; D013997:Time Factors
D000081:Acetamides; C014026:hexamethylene bisacetamide