The Clinical Pharmacology of Antineoplastic Agents

5-Fluorouracil Concentrations in Rat Plasma, Parotid Saliva, and Bile and Protein Binding in Rat Plasma

“…The fact that surface activity may play a role in the mechanism of action of some drugs is evident from the correlations obtained (2) between surface activity and biological effects. Previous researchers (3) have concluded that in the case of psychotropic drugs, surface activity is the primary factor which determines their potency and not the specific chemical structure.…”

“…the synthesis of DNA (l), is extensively used in the treatment of neoplasms of the breast and GI tract (2), with a trend toward utilizing it in combination with several chemotherapeutic agents in complex schedules for disseminated disease (3)(4)(5). Information concerning the concentration-time course in plasma and body excretions may be helpful in establishing dose schedules with a pharmacological rationale.…”

Is there a role for thymidine in cancer chemotherapy?

“…I~ cytostatic ac~on has been attdbuted to i~ tfiphosphate, ara-~P, The c0nve~ion of a~-C to ara-~P is mediated by d~xycyfidine kinase (14), The~: ~ evidence that dCTP inhibi~ the intracellular fo~afion ofara-C~P probably by inhibiting deoxycyddine kinase (86)+ H r, most offhe growth-inhibitory e-lTect ofara-C depends on the amount ofint~cellular ara-CTP in ~lation to the cellular content ofdCTP (103, 39)+ As TdR inhibits dC~TP formation by inhibition of Hbonudeodde reductase (54), a combination ofTdR ~th ara-C might theoreti~lly enhance the sensitivity ofthe+.celts for the latter d~g. Following this hypothe~, Harris a aL could show an increased sensitivity of 2 lymphoid cell lin~ to a~-C in vitro when combined with 10 ~ ~ TdR (39)+ Thee findin~ have been confirmed by other invesfigato~ (8, 2l, 89, I01)+ Another aspect of ara-C action is i~ inhibition of repair of single-strand DNA brea~ induced by ultraviolet irradiation, which has been shown by Johnson and Collins and by Dunn and Regan (23, 57)+ Woodcock et aL have presented evidence that ara-C can induce re.initiation of DNA synth~is in DNA segmen~ which had been replicated easier in the same S phase (110, 111)+ Thus, under the influence of ara-C under ~rtain conditions some DNA se~ents undergo double replication during a single S phase.…”

Radioimmunoassay of drugs and its clinical application

“…It is a "natural" product containing a number of closely related substances all possessing similar anti-tumour activity. The appearance of unpredictable side effects such as pulmonary toxicity has limited the clinical use of bleomycin (67). These toxic effects are more common in some parts of the world than in others and may reflect subtle differences between the different bleomycin preparations available.…”