In vivo absorption study of ritodrine hydrochloride in the buccal administration to rats.
BACKGROUND
Although ritodrine (RD)-hydrochloride (HCl), named RD-HCl, is widely used in the treatment of premature labor by intravenous prolonged infusion or frequent oral dosing of tablets, those administrations often lower patients' quality of life (QOL) or cause undesirable side effects, such as tachycardia; therefore, in this study, the potential usefulness of buccal administration as a novel administration method was examined in vivo.


METHODS
First, the HPLC method was assessed for the determination of plasma RD concentration. Then, after RD-HCl solution in saline was administered intravenously (1 mg/kg), intragastrically (10 mg/kg) or buccally (10 mg/kg) in rats, the plasma concentration-time profiles were investigated, and the absorption extent and rate compared.


RESULTS
The present modified determination method by HPLC with fluorescence detection (Ex. 278 nm, Em. 306 nm) was suitable to analyze the plasma level at 8-200 ng/mL. Buccal administration gave the best plasma concentration-time profile for maintenance of an effective plasma level and fewer side effects. Absorption rates calculated by deconvolution also supported better sustained absorption in buccal dosing.


CONCLUSIONS
Buccal application of RD-HCl was demonstrated to be a potentially useful dosing method in the treatment of premature labor with RD-HCl.
Department of Drug Delivery Research, Hoshi University, Ebara, Shinagawa-ku, Tokyo, Japan.
Osamu
O
Sakata
Hiraku
H
Onishi
D000042:Absorption; D000278:Administration, Buccal; D000284:Administration, Oral; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000465:Algorithms; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D009061:Mouth Mucosa / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012312:Ritodrine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D012995:Solubility; D013050:Spectrometry, Fluorescence; D015149:Tocolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
D058666:Adrenergic beta-2 Receptor Agonists; D015149:Tocolytic Agents; D012312:Ritodrine