In vivo assessment of salmon calcitonin sustained release from biodegradable microspheres

Lee, K.C.; Soltis, Edward E.; Newman, Pamela S.; Burton, K. W.; Mehta, Rahul; DeLuca, Patrick P.

doi:10.1016/0168-3659(91)90059-m

Cited by 42 publications

(15 citation statements)

References 5 publications

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“…Although the relatively normal value for CT-treated OVX rats suggests that these animals were not hypocalcemic, it is important to note that the terminal blood samples were collected at least 24 hours after the last CT injection. Therefore, the possibility that CT induced a transient hypocalcemia of 2-3 hours duration after an S.C. injection [25] cannot be ruled out. Cancellous bone volume of vehicle-treated control rats remained relatively constant over the entire study (Fig.…”

Section: Resultsmentioning

confidence: 97%

Skeletal effects of calcitonin treatment and withdrawal in ovariectomized rats

Shen

Wronski

1996

Calcif Tissue Int

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The study was designed to determine, by histomorphometric techniques, bone changes as a function of time during long-term treatment with salmon calcitonin (CT) and after withdrawal of the hormone in ovariectomized (OVX) rats. Groups of OVX rats were treated with vehicle alone or CT on alternate days for 30, 60, or 90 days. Additional groups of sham-operated control rats were treated with vehicle alone. Rats from each of the three groups were sacrificed at each time point. All treatments in the remaining rats were then terminated at 90 days, followed by sacrifice of rats from each group at 30 and 60 days after withdrawal of vehicle or CT treatment. The proximal tibia from each animal was processed undecalcified for quantitative bone histomorphometry. Compared with control rats, the proximal tibiae of vehicle-treated OVX rats were characterized by cancellous osteopenia and significant increases in osteoclast surface, osteoblast surface, mineralizing surface, mineral apposition rate, and bone formation rate. CT treatment of OVX rats partially prevented cancellous bone loss by approximately 50% and significantly decreased most of the above indices of bone turnover relative to vehicle-treated OVX rats. However, soon after withdrawal of CT, OVX rats previously treated with the hormone exhibited rapid loss of cancellous bone associated with increased bone turnover. These results in an animal model of estrogen depletion suggest that early postmenopausal women who are withdrawn from prophylactic CT treatment may be at high risk for subsequent bone loss.

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Section: Resultsmentioning

confidence: 97%

Skeletal effects of calcitonin treatment and withdrawal in ovariectomized rats

Shen

Wronski

1996

Calcif Tissue Int

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“…2,3) However, the bioavailability is still low even if CT was intranasally administered with absorption enhancers. Although PA has often been used to assess the absorption of sCT, [8][9][10] the hypocalcemic eŠect of sCT is a result of summation of multiple actions of sCT, endogenous CT, parathyroid hormone (PTH), 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3)a n d other calcitropic factors. trypsin, aminopeptidase) in the nasal mucosa.…”

Section: Introductionmentioning

confidence: 99%

Estimation of Bioavailability of Salmon Calcitonin from the Hypocalcemic Effect in Rats (I): Pharmacokinetic-Pharmacodynamic Modeling Based on the Endogenous Ca Regulatory System

Miyazaki

Nakade

Iwanaga

et al. 2003

Drug Metabolism and Pharmacokinetics

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The hypocalcemic effect of salmon calcitonin (sCT) after intravenous administration was explained on the basis of an integrated pharmacokinetic-pharmacodynamic (PK-PD) model with the endogenous Ca regulatory system in the rat. The pharmacokinetics of sCT described by a conventional two-compartment model showed the extremely rapid elimination of sCT from plasma (MRT; 6.86 min). The hypocalcemic effect of sCT reached a peak from 0.5 to 1.5 hrs after administration, and the peak time tended to prolong with increasing doses. This delay in pharmacological effect of sCT against plasma concentration may be a result of a summation of multiple actions of the endogenous Ca regulatory system including feedback control. The plasma Ca regulation system in the rat was investigated by i.v. bolus administration of calcium gluconate and/or endogenous (rat) calcitonin (rCT). Since non-linearity in the relationship between Ca and rCT concentrations in plasma was observed, we assumed that rCT was secreted in accordance with the plasma Ca level via an exponential function. The pharmacokinetics of rCT was represented as a linear one-compartment model. To link the rCT level with plasma Ca level, an additional effect compartment was required to explain the delay in onset and decline of the pharmacological effect. This Ca regulation model explained the observed Ca and rCT profiles in plasma after administration of Ca and/or rCT. The plasma Ca levels after administration of sCT could be well described by the present integrated model. This suggested the potential for prediction of plasma sCT concentration only from the hypocalcemic effect after extravascular administration of sCT, using this PK-PD model.

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“…Extended release of peptides from such depot formulations is dependent on several factors [36][37][38][39][40]. Depending on the period of delivery, enough compound has to be incorporated into the polymer.…”

Section: Formulation Studiesmentioning

confidence: 99%