title: Effects of molecular mass and hydrophobicity on transport rates through non-specific pathways of the silkworm larva midgut.
abstract: We previously reported that therapeutic drug effects in the silkworm infection model are largely influenced by midgut permeability. In this report, we describe the effects of drug molecular mass and hydrophobicity on transport through the silkworm larva midgut membrane. Hydrophilic compounds with a molecular mass of greater than 400Da did not permeate the silkworm larva midgut, and the hydrophobicity of similar-sized compounds had positive effects on the transport rate. Furthermore, we compared transport rates through the midgut membrane between cefcapene sodium (CFPN-Na) and cefcapene pivoxil (CFPN-PI), which is a CFPN-Na prodrug. The in vitro transport rate of CFPN-PI was three times faster than that of CFPN-Na. Moreover, when CFPN-PI and CFPN-Na were injected into the living silkworm larva midgut, CFPN-PI appeared rapidly in the haemolymph, whereas CFPN-Na did not. The 50% effective dose (ED50) of CFPN-PI administered via the midgut was one-sixth that of CFPN-Na. These findings suggest that the general features of the non-specific transport route are similar between silkworm larvae and mammals.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 3-1, 7-Chome, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamamoto
authors.forename: Koushirou
authors.initials: K
authors.lastname: Kamura
authors.forename: Iony Manitra
authors.initials: IM
authors.lastname: Razanajatovo
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Murakami
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Santa
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sekimizu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001692:Biological Transport; D012831:Bombyx / Q000378:metabolism*; D002511:Cephalosporins / Q000493:pharmacokinetics; D041981:Gastrointestinal Tract / Q000378:metabolism; D007408:Intestinal Absorption; D007814:Larva / Q000378:metabolism; D023421:Models, Animal; D008970:Molecular Weight; D011355:Prodrugs / Q000493:pharmacokinetics; D012995:Solubility
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D011355:Prodrugs; C425944:cefcapene pivoxil hydrochloride