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Administration of follitropin alfa and lutropin alfa combined in a single injection: a feasibility assessment

BACKGROUND: Gonadotrophins are routinely administered in assisted reproductive technology (ART) treatment protocols. Recombinant human follicle-stimulating hormone (r-hFSH; follitropin alfa) and recombinant human luteinizing hormone (r-hLH; lutropin alfa) can be administered individually or in a fix...

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Autor principal: Agostinetto, Rita
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688505/
https://www.ncbi.nlm.nih.gov/pubmed/19450267
http://dx.doi.org/10.1186/1477-7827-7-48
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author Agostinetto, Rita
author_facet Agostinetto, Rita
author_sort Agostinetto, Rita
collection PubMed
description BACKGROUND: Gonadotrophins are routinely administered in assisted reproductive technology (ART) treatment protocols. Recombinant human follicle-stimulating hormone (r-hFSH; follitropin alfa) and recombinant human luteinizing hormone (r-hLH; lutropin alfa) can be administered individually or in a fixed combination. The ability to vary the FSH to LH dose ratio in a single injection without compromising the bioactivity of either gonadotrophin or generating losses of active principle is important for physicians and patients alike. METHODS: This study investigated whether follitropin alfa (GONAL-f (R)), as lyophilized powder for reconstitution or solution from the GONAL-f (R) (filled-by-mass [FbM]) Prefilled Pen, could be used to reconstitute Pergoveris TM (follitropin alfa/lutropin alfa 150 IU/75 IU) lyophilized powder. In Ratio Groups 1 and 2, the r-hFSH:r-hLH ratio was 3:1; in Ratio Groups 3 and 4, the ratios of r-hFSH:r-hLH were 5:1 and 8:1, respectively. The protein content and bioactivity of each mixed solution were evaluated. The r-hFSH and r-hLH content was determined using reverse-phase high performance liquid chromatography. The biological activity of r-hFSH and r-hLH was assessed using the Steelman-Pohley and Van Hell in vivo bioassays in rats, respectively. RESULTS: Follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder could be successfully mixed with follitropin alfa 75 IU FbM solution that was either reconstituted from lyophilized powder or injected directly from the prefilled pen to create solutions with ratios of r-hFSH and r-hLH from 3:1 to 8:1. The measured content of r-hFSH and r-hLH corresponded favourably with the target protein content in Ratio Groups 1–4. The in vivo target and measured bioactivity of r-hFSH and r-hLH were also closely matched in all Ratio Groups. CONCLUSION: Follitropin alfa lyophilized powder or solution can be accurately mixed with follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder to enable physicians to administer ratios of r-hFSH and r-hLH in the IU range from 3:1 to 8:1. Mixing of recombinant formulations offers flexibility for patients receiving follitropin alfa and lutropin alfa for ART protocols in clinical practice.
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spelling pubmed-26885052009-05-30 Administration of follitropin alfa and lutropin alfa combined in a single injection: a feasibility assessment Agostinetto, Rita Reprod Biol Endocrinol Research BACKGROUND: Gonadotrophins are routinely administered in assisted reproductive technology (ART) treatment protocols. Recombinant human follicle-stimulating hormone (r-hFSH; follitropin alfa) and recombinant human luteinizing hormone (r-hLH; lutropin alfa) can be administered individually or in a fixed combination. The ability to vary the FSH to LH dose ratio in a single injection without compromising the bioactivity of either gonadotrophin or generating losses of active principle is important for physicians and patients alike. METHODS: This study investigated whether follitropin alfa (GONAL-f (R)), as lyophilized powder for reconstitution or solution from the GONAL-f (R) (filled-by-mass [FbM]) Prefilled Pen, could be used to reconstitute Pergoveris TM (follitropin alfa/lutropin alfa 150 IU/75 IU) lyophilized powder. In Ratio Groups 1 and 2, the r-hFSH:r-hLH ratio was 3:1; in Ratio Groups 3 and 4, the ratios of r-hFSH:r-hLH were 5:1 and 8:1, respectively. The protein content and bioactivity of each mixed solution were evaluated. The r-hFSH and r-hLH content was determined using reverse-phase high performance liquid chromatography. The biological activity of r-hFSH and r-hLH was assessed using the Steelman-Pohley and Van Hell in vivo bioassays in rats, respectively. RESULTS: Follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder could be successfully mixed with follitropin alfa 75 IU FbM solution that was either reconstituted from lyophilized powder or injected directly from the prefilled pen to create solutions with ratios of r-hFSH and r-hLH from 3:1 to 8:1. The measured content of r-hFSH and r-hLH corresponded favourably with the target protein content in Ratio Groups 1–4. The in vivo target and measured bioactivity of r-hFSH and r-hLH were also closely matched in all Ratio Groups. CONCLUSION: Follitropin alfa lyophilized powder or solution can be accurately mixed with follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder to enable physicians to administer ratios of r-hFSH and r-hLH in the IU range from 3:1 to 8:1. Mixing of recombinant formulations offers flexibility for patients receiving follitropin alfa and lutropin alfa for ART protocols in clinical practice. BioMed Central 2009-05-18 /pmc/articles/PMC2688505/ /pubmed/19450267 http://dx.doi.org/10.1186/1477-7827-7-48 Text en Copyright © 2009 Agostinetto; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Agostinetto, Rita
Administration of follitropin alfa and lutropin alfa combined in a single injection: a feasibility assessment
title Administration of follitropin alfa and lutropin alfa combined in a single injection: a feasibility assessment
title_full Administration of follitropin alfa and lutropin alfa combined in a single injection: a feasibility assessment
title_fullStr Administration of follitropin alfa and lutropin alfa combined in a single injection: a feasibility assessment
title_full_unstemmed Administration of follitropin alfa and lutropin alfa combined in a single injection: a feasibility assessment
title_short Administration of follitropin alfa and lutropin alfa combined in a single injection: a feasibility assessment
title_sort administration of follitropin alfa and lutropin alfa combined in a single injection: a feasibility assessment
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688505/
https://www.ncbi.nlm.nih.gov/pubmed/19450267
http://dx.doi.org/10.1186/1477-7827-7-48
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