In vivo iontophoretic delivery and pharmacokinetics of salmon calcitonin.
In vivo iontophoretic delivery of salmon calcitonin (SCT) in hairless rats using a self-contained wearable and disposable iontophoretic patch was investigated. Iontophoretic patches with built-in proprietary Zn/AgCl electrodes were used. SCT was formulated in citrate buffer (50mM, pH 4.0) to impart a positive charge for anodal iontophoresis. SCT was delivered intravenously to determine primary pharmacokinetic parameters. Pharmacokinetics of iontophoretic delivery of SCT was compared with subcutaneous route of administration. Blood samples were collected through tail vein and analyzed for serum SCT and calcium levels. Pharmacokinetic parameters were calculated by non-compartmental analysis. An average current of 0.43+/-0.01 mA was maintained during patch application. Iontophoretic patches delivered SCT at an average infusion rate of 177.9+/-58.7 ng/(min kg) and an average steady state concentration of 7.58+/-1.35 ng/ml was achieved. There was no difference between the calcium lowering effect of iontophoretic patch and subcutaneous injection (p>0.05). Clearance and half-life of SCT after IV administration were found to be 16.8+/-0.9 ml/(min kg) and 33.5+/-3.3 min, respectively. The iontophoretic delivery of SCT was well defined by a one-compartment model with zero-order infusion. Iontophoretic patch delivered therapeutically relevant concentrations of SCT in hairless rats and delivery was comparable to conventional routes.
Chaturvedula
Ayyappa
A
Department of Pharmaceutical Sciences, 3001 Mercer University Drive, Mercer University, Atlanta, GA 30341, USA.
Joshi
Dipty P
DP
Anderson
Carter
C
Morris
Russell L
RL
Sembrowich
Walter L
WL
Banga
Ajay K
AK
D000818:Animals; D019540:Area Under Curve; D002116:Calcitonin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002118:Calcium / Q000097:blood; D016503:Drug Delivery Systems; D004563:Electrochemistry; D004566:Electrodes; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007478:Iontophoresis; D008297:Male; D051381:Rats
C028815:salmon calcitonin; D002116:Calcitonin; D002118:Calcium