Absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) from rat nasal mucosa.
Nasal absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was examined in the rat. The relative bioavailability of rhG-CSF for subcutaneous administration was approximately 2%, as evaluated from the immunologically active rhG-CSF concentration in rat plasma and the area under the curve (AUC) of the plasma rhG-CSF concentration versus time for 8 hr. Pharmacological availability relative to subcutaneous administration was determined from the increase in total blood leukocyte numbers. The pharmacological availability was 5-10%, determined from the AUC for the increased ratio of total leukocyte numbers versus time for 48 hr; it was slightly dependent on the pH and the osmotic pressure of the dosing solution. Accordingly, the plasma concentration of rhG-CSF did not always reflect its pharmacological effects. Relative bioavailability and pharmacological availability were increased about 23 times and 3 times, respectively, by polyoxyethylene 9-lauryl ether (Laureth-9), but no increase in availability occurred with sodium glycocholate. The increase in total leukocyte numbers was maintained during multiple rhG-CSF dosing, and the addition of Laureth-9 further increased the pharmacological effects of this agent. This study indicates that nasal administration of rhG-CSF is an effective parenteral administration route.
Machida
M
M
Formulation Technology Laboratory, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
Sano
K
K
Arakawa
M
M
Hayashi
M
M
Awazu
S
S
D000042:Absorption; D000281:Administration, Intranasal; D000818:Animals; D001682:Biological Availability; D005079:Excipients; D016179:Granulocyte Colony-Stimulating Factor / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000494:pharmacology; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics / Q000494:pharmacology
D005079:Excipients; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor