Relative bioavailability of two drug products of somatropin obtained from either the milk of transgenic cows or bacterial culture.
BACKGROUND
Our objective was to assess the relative bioavailability of the first somatropin produced in transgenic cloned cows that carry the human growth hormone (GH) gene (Biohormon) and somatropin produced in Escherichia coli culture (HHT), the procedure most frequently used for the commercial production of the hormone.


METHODS
Upon approval by an independent ethics committee and the National Regulatory Agency of Argentina, we compared the time-concentration profiles of somatropin in 24 healthy volunteers, in a randomized, 2-period, 2-sequence crossover design after inhibition of endogenous GH secretion with lanreotide, a long-acting somastostatin analogue. After the subcutaneous administration of 1.33 mg of each formulation, serum somatropin was analyzed by chemiluminescent immunoassay and IGF-I by immunoradiometric assay. Safety was assessed by clinical and laboratory parameters. Pharmacokinetic parameters were calculated with Win Nonlin 5.2 using a non-compartmental model and bioequivalence was assessed.


RESULTS
The test/reference ratios of AUC, AUC(last) and C(max) were 106.4 (90% CI = 100.2-112.9), 105.3 (90% CI = 99.1-111.8) and 105.49 (90% CI = 92.6-120.1), respectively. No serious adverse events were reported and no GH antibodies were detected.


CONCLUSIONS
This study demonstrates that a single dose of Biohormon, the first product with somatropin obtained from milk of transgenic mammals, is bioequivalent to the reference product HHT according to standard criteria.
Farías
J
J
Bio Sidus SA, Buenos Aires, Argentina. javiermfarias @ arnet.com.ar
Feleder
E
E
González
E
E
Halabe
K
K
Criscuolo
M E
ME
Bergadá
I
I
Diez
R A
RA
D000328:Adult; D000818:Animals; D030801:Animals, Genetically Modified; D019540:Area Under Curve; D001682:Biological Availability; D002417:Cattle; D018592:Cross-Over Studies; D004393:Dwarfism, Pituitary / Q000378:metabolism / Q000628:therapy; D005260:Female; D013006:Growth Hormone / Q000096:biosynthesis / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D020249:Hormone Replacement Therapy / Q000379:methods; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008892:Milk / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000097:blood / Q000493:pharmacokinetics*
D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone