Cyclosporine metabolism and pharmacokinetics following intravenous and oral administration in the dog

Bruno Gridelli, Lenia Scanlon, Riccardo Pellicci, Real Lapointe, Andre Dewolf, Howard Seltman, Warren Diven, Byers Wendell Shaw Jr, Thomas Starzl, Ajit Sanghvi

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

The influence of assay method on single dose cyclosporine (CsA) pharmacokinetics was studied in nine dogs receiving either i.v. or oral CsA. Samples were drawn from hepatic, portal, and systemic veins at various times after the dose and CsA levels were determined by radiommunoassay (RIA) and high-performance liquid chromatography (HPLC). Blood concentration-time data were analyzed by nonlinear least-squares regression, using two-compartment models. RIA/HPLC ratios for all samples were greater than one, and did not change significantly over time. The mean RIA/HPLC ratios for samples drawn from all three veins were higher after oral than i.v. doses of the drug (T="I">P<0.05). Area under the concentration-time curve (AUC) was higher and systemic clearance (Cls) lower than calculated on the basis of RIA results, regardless of the route of administration. AUC calculated for CsA metabolites (RIA-HPLC) was highest in the portal vein after an oral dose of CsA. Bioavailability was 20.4% and 27.0% when estimated using HPLC and RIA data, respectively. The mean CsA metabolite index (CMI), when calculated for hepatic, portal, or systemic vein, was greater when the drug was administered orally. The mean hepatic extraction ratio (HER) of the parent drug and for CsA metabolites was approximately 23% in i.v. and p.o. studies. These results suggest that the gastrointestinal tract may play a role in the metabolism of CsA when the drug is administered orally. In addition, if CsA metabolites not measured by HPLC have either toxic or immunosuppressive properties, the RIA assay may be more useful for monitoring patients.

Original languageEnglish (US)
Pages (from-to)388-391
Number of pages4
JournalTransplantation
Volume41
Issue number3
DOIs
StatePublished - Jan 1 1986

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Intravenous Administration
Cyclosporine
Oral Administration
Pharmacokinetics
High Pressure Liquid Chromatography
Dogs
Portal Vein
Pharmaceutical Preparations
Veins
Liver
Poisons
Physiologic Monitoring
Immunosuppressive Agents
Least-Squares Analysis
Biological Availability
Gastrointestinal Tract

ASJC Scopus subject areas

  • Transplantation

Cite this

Gridelli, B., Scanlon, L., Pellicci, R., Lapointe, R., Dewolf, A., Seltman, H., ... Sanghvi, A. (1986). Cyclosporine metabolism and pharmacokinetics following intravenous and oral administration in the dog. Transplantation, 41(3), 388-391. https://doi.org/10.1097/00007890-198603000-00021

Cyclosporine metabolism and pharmacokinetics following intravenous and oral administration in the dog. / Gridelli, Bruno; Scanlon, Lenia; Pellicci, Riccardo; Lapointe, Real; Dewolf, Andre; Seltman, Howard; Diven, Warren; Shaw Jr, Byers Wendell; Starzl, Thomas; Sanghvi, Ajit.

In: Transplantation, Vol. 41, No. 3, 01.01.1986, p. 388-391.

Research output: Contribution to journalArticle

Gridelli, B, Scanlon, L, Pellicci, R, Lapointe, R, Dewolf, A, Seltman, H, Diven, W, Shaw Jr, BW, Starzl, T & Sanghvi, A 1986, 'Cyclosporine metabolism and pharmacokinetics following intravenous and oral administration in the dog', Transplantation, vol. 41, no. 3, pp. 388-391. https://doi.org/10.1097/00007890-198603000-00021
Gridelli, Bruno ; Scanlon, Lenia ; Pellicci, Riccardo ; Lapointe, Real ; Dewolf, Andre ; Seltman, Howard ; Diven, Warren ; Shaw Jr, Byers Wendell ; Starzl, Thomas ; Sanghvi, Ajit. / Cyclosporine metabolism and pharmacokinetics following intravenous and oral administration in the dog. In: Transplantation. 1986 ; Vol. 41, No. 3. pp. 388-391.
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