The systemic absorption of etoposide after intravaginal administration in patients with cervical intraepithelial lesions associated with human papillomavirus infection.
OBJECTIVE
The purpose of this study was to determine the systemic absorption and the release of etoposide in cervical tissue administered via a vaginal ovule to women diagnosed with cervical intraepithelial lesions associated with human papillomavirus (HPV).


METHODS
Fifteen women with low- and high-grade intraepithelial neoplasia confirmed by colposcopic test received a 50-mg intravaginal etoposide dose three times a week for 3 weeks. At the end of the study period, paralleled with the last ovule administered, blood samples were collected over a period of 24 h, and in situ cervical samples were obtained at 3 and 10 h after drug administration. Etoposide concentrations were determined in plasma and in in situ cervical samples using the high-performance liquid chromatography method with electrochemical detection.


RESULTS
Pharmacokinetic analyses of plasma data indicated low or lack of systemic exposure of etoposide after the vaginal administration. Nevertheless, high concentrations of etoposide were found in all in situ cervical samples, indicating that etoposide could be released from its pharmaceutical formulation.


CONCLUSIONS
The results of the study suggest that the etoposide administered as intravaginal ovule is safe and tolerable and apparently could be a suitable option in patients with cervical intraepithelial neoplasia. Clinical results and the true impact on HPV infection and evolution of dysplasia need to be confirmed.
García-López
P
P
División de Investigación Básica, Instituto Nacional de Cancerología, INCan, Av. San Fernando # 22 Tlalpan, 14000 México, D.F., México. pgarcia_lopez@yahoo.com.mx
Coll
M
M
Cervera
E
E
Reyes-Vermot
L
L
Torres
M A
MA
Abrego-Pérez
G
G
Hernández-Pájaro
A I
AI
Castañeda-Hernandez
G
G
Mohar-Betancourt
A
A
Meneses
A
A
D000042:Absorption; D000282:Administration, Intravaginal; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000188:drug therapy*; D011446:Prospective Studies
D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D005047:Etoposide