Serum and tissue levels of platinum after cisplatinum instillation of the rat bladder.
The absorption of chemotherapeutics after local application in the urinary bladder is important for optimum therapy. We therefore investigated the absorption of Cisplatinum (Pt) through the bladder wall in 100 female Sprague-Dawley-rats after instillation under different clinical and pharmacological conditions. Only low platinum (Pt)-concentrations of about 1 microgram/ml could be detected in the serum using unmodified Cisplatinum solutions for instillation in the rat bladder indicating a rather low absorption rate for Cisplatinum. The extent of the absorption of Cisplatinum through the instilled bladder increased with the instilled volume. The absorption rate also increased after electrocoagulation and during cystitis with a maximum concentration of about 2.64 micrograms/ml. Correspondingly the vesicoplasmatic gradient factor clearly decreased. On addition of the detergent Tween 80, the serum Pt-concentration increased rapidly during the initial 30 min. Under these conditions Cisplatinum penetrated the bladder wall, about three times more effectively than in the absence of Tween while entering the systemic circulation only at about twice the normal rate without Tween 80. On addition of the polar organic solvent dimethylsulfoxide (DMSO) serum Pt-concentration increased continuously during the following 2 to 3 h reaching maximum values of about 13.3 micrograms/ml. The greatest accumulation of Pt in the bladder tissue (about 1,600 micrograms Pt/g tissue) was also observed under these conditions. A comparison of the Pt-concentration in serum with that in the bladder wall showed the most favourable relation of high tissue penetration and low serum concentration using Tween 80.
Wagner
H A
HA
Department of Clinical Chemistry, University of Göttingen, Federal Republic of Germany.
Groebe
G
G
Engelmann
U
U
D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003556:Cystitis / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004564:Electrocoagulation; D005260:Female; D010984:Platinum / Q000032:analysis* / Q000097:blood; D011136:Polysorbates; D051381:Rats; D011919:Rats, Inbred Strains; D001743:Urinary Bladder
D011136:Polysorbates; D010984:Platinum; D002945:Cisplatin; D004121:Dimethyl Sulfoxide