Cisplatin suppository: preparation, release characteristics and clinical evaluation.
Cisplatin (CDDP) has attracted attention as a chemotherapeutic agent for the treatment of uterine endometrial carcinoma but causes serious side effects, including renal toxicity. CDDP suppositories containing NaCl at different concentrations were prepared to enhance the efficacy and to reduce the side effects of CDDP. The release characteristics, melting point and viscosity of the suppositories were first studied. The rate of CDDP release increased as the NaCl concentration increased: it was 12% 12 h after administration of suppositories containing no NaCl, but 32% with 0.2% NaCl. The melting point was raised by addition of NaCl: 35.5 degrees C without NaCl and 36.5 degrees C with 0.2% NaCl. Addition of 0.2% NaCl doubled the viscosity. Clinically, the suppository containing 0.06% NaCl was given to 3 patients with endometrial carcinoma twice a week for 3 weeks to examine serum CDDP levels and endometrial absorption. Patients with endometrial carcinoma showed different peak plasma platinum (Pt) levels which were as low as 0.12, 0.06 and 0.22 micrograms Pt/ml with similar patterns of change in the level. Radiographic analysis revealed many Pt particles in sections of necrosed endometria after 21d of the treatment. No side effects of CDDP were found in biochemical testing or subjective symptoms.
Department of Pharmacy, Kochi Medical School Hospital, Japan.
Y
Y
Nishioka
S
S
Kyotani
M
M
Kusunose
H
H
Mimoto
T
T
Hamada
M
M
Asai
Y
Y
Sagara
D000368:Aged; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016889:Endometrial Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D013488:Suppositories
D013488:Suppositories; D002945:Cisplatin