Non-clinical Pharmacokinetic And Pharmacodynamic Study Of An Oral Insulin Enteric Capsule

AIM: To study the non-clinical pharmacokinetics (PK) and pharmacodynamics (PD) oforal insulin enteric capsule.METHODS: The euglycemic clamp technique was employed to study the PD propertyof the oral insulin enteric capsule in beagles, while the PK profile of the drug wasevaluated by a radioimmunoassay (RIA) method at the same time. The method ofradiolabeled tracer coupled with SHPLC and TCA precipitation was utilized to observeabsorption, biodistribution, and excretion of the oral insulin enteric capsule and thenanoparticle (NP) cartier in rats.RESULTS AND CONCLUSIONS: 1. Oral insulin enteric capsule was associated withslower uptake and later onset of action, lower GIR_max and C_max, but a longer duration ofaction, compared with sc regular insulin. 2. After oral administration, relative biologicalavailability and bioefficacy of the oral insulin enteric capsule were 17.5ï¼…and 18.8ï¼…,respectively, compared with sc regular insulin. Both the biological availability andbioefficacy were significantly higher than that after po crude insulin. 3. The increase ofdosage level (3 times) of the oral insulin enteric capsule contributed a delayed T_max andT_GIRmax, however the C_max and GIR_max had no significant difference compared with theopposite dosage level. 4. Rapid individual diversity of the animals was represented inboth PK and PD study after oral administration. 5. The tissue distribution profiles ofinsulin (traced by ¹²⁵I) and NP carrier (traced by ³²p) were quite similar. Radioactivitydistributed predominantly in urine, intestinal content, bladder, serum, kidney, small intestine, and liver, et al. 6. The radioactivity was comparatively low in brain, suggestedinsulin and NP carrier could hardly get across the blood-brain barrier. 7. Theradioactivity was excreted mainly via the urinary system, and little via bile and fecesroutes. 8. There were lots of nanoparticles in ileum, suggested that NPs might beabsorbed mainly in ileum.