Possible Interaction: Cisplatin and Procaine

“An increase in the survival of patients suffering from disseminated lymphosarcomas and treated with a combination of cisplatin and procaine , as compared with those treated with cisplatin alone, has been reported (Qiao 1982).”

“Combined treatment of cisplatin and P.HCl greatly attenuated morphological alterations of the rat kidney and reduced the changes in enzyme activities, except for NOS/NADPHd activity, compared to the cisplatin-treated group of animals.”

“The local anesthetic procaine hydrochloride P.HCl ) improves the therapeutic index of cisplatin not only by the reduction of its nephro- and hemotoxicity, but also by an increase of its antitumor activity.”

“The study indicates that, in cisplatin-induced nephrotoxicity, a significant role is played by enzyme activities, in particular K+ pNPPase and NOS/NADPHd, and that P.HCl can mitigate the nephrotoxicity of cisplatin , possibly by influencing some enzyme activities involved in important renal metabolic pathways.”

“In conclusion procaine hydrochloride increased the antitumor activity of cisplatin independently from its timing of administration, although it seemed to be a better potentiating agent when administered after cisplatin.”

“In previous papers (1,2) we demonstrated that procaine hydrochloride may increase the therapeutic index of cisplatin by an improvement of its antitumor activity and a reduction of its nephrotoxicity.”

“In the present study we investigated the relationship between the antitumor activity obtained by cisplatin associated with procaine hydrochloride and the relative time of administration of these two agents.”

“These results became statistically significant when procaine hydrochloride was given either simultaneously with cisplatin or 30 and 120 minutes thereafter (%ILS: > 400 vs +150; cure rate: 65.4%, 73.1% and 68% vs 23%, respectively).”

“… procaine hydrochloride (40 mg/Kg … minutes before cisplatin (16 mg/kg) diluted in normal saline (i.e. clinical condition) it increased, although not significantly, its percent increase in life …: +292 and +217 vs +150; cure rate: 46.2% and 42.3% vs 23%, respectively), compared to cisplatin alone treatment.”

“1 Procaine has previously been shown to diminish the nephrotoxicity of cisplatin and the nephrotoxic effects of cisplatin and a new cisplatin complex (cis-diammine chloro - [2 - (diethylamino) ethyl - 4 - aminobenzoate, N4]- chlorideplatinum (II) monohydrochloride monohydrate; DPR), that contains procaine hydrochloride were com pared with rat renal cortical slices.”

“Since procaine , which differs from Pd merely in the replacement of the amide by the ester linkage, has also been reported to significantly enhance DDP efficacy (M. Esposito et al., 1990, J. Natl.”

“A statistically significant reduction of kidney and spleen Pt content was observed in female mice exposed to a dose of 8 mg/kg DDP + P.HCl.”

“Potential explanations for the ability of P.HCl to interfere with the pharmacokinetics and biodistribution of DDP are discussed.”

“The unbound fraction of Pt was significantly increased both in the ascites fluid and plasma following DDP + P.HCl administration.”

“The ability of procaine hydrochloride (P.HCl) to modulate the effects of cisplatin (DDP) on pluripotent (CFU-S) and committed (CFU-GM) murine hemopoietic stem cells was investigated.”

“The simultaneous administration of the lower DDP dose together with P.HCl greatly reduced the hemotoxicity of the antitumoral drug, while this protection was not significant with the higher DDP dose.”

“Protection from DDP nephrotoxicity seems to be the explanation for the higher doses of DDP that mice can tolerate when DDP is given simultaneously with P.HCl.”

“The local anesthetic procaine hydrochloride (P.HCl) had little effect on the … cells to cisplatin (DDP) in vitro, but the simultaneous administration of DDP … P.HCl (40 mg/kg) to BDF1 mice produced 50% lethal dose (LD50) and …) values approximately two times higher than those observed with DDP alone.”

“ Cisplatin also increased mitochondrial lipid peroxidation to 177% of controls, and procaine , DEAE and PABA inhibited this cisplatin-induced increase by 24, 30 and 22%, respectively.”

“ Procaine (2 mm) protected against this cellular damage and decreased the leakage to 50, 65 and 29% of that caused by cisplatin.”

“These observations suggest that the protection by procaine and its metabolites results from their inhibitory activity on the mitochondrial lipid peroxidation that was induced by cisplatin.”