Author/Editor		Mrhar, A; Karba, R; Grabnar, I; Belič, A; Vojnović, D; Chicco, D
Title		Physiologically applicable compartment model as a tool for explication of paracetamol rectal availability
Type		članek
Source		In: Ashton-Miller JA, editor. Proceedings of the 10th international conference on mechanics in medicine and biology; 1998 Mar 2-5; Waikiki, Honolulu. Waikiki: Pacific centre of thermal-fluids engineering (PCTFE),
Publication year		1998
Volume		str. 347-50
Language		eng
Abstract		An approach based on modeling and simulation was chosen to explain rectal availability of paracetamol, which is an effective analgesic and antipyretic for the treatment of minor, noninflamatory conditions. In Vitro release curves which were differentiated and adaptable to therapeutic conditions were obtained by vehicling paracemtal in suppositories of the two superimposed layers of lipophilic excipients with different hydroxyl value and hence with a difference in paracetamol availability. Two types of suppositories were from the tested batches: instant release, lower hydroxyl value (firmulation A) and sustained release, higher hydroxyl value (formulation B). Suppositories were given in an In Vivo randomized and crossover trial to 5 healthy volunteers to obtain by the use of specific HPLC analytical method paracetamol profiles in plasma and urine and profile of paracetamol metabolites excreted in urine. The resulting In Vitro release curve exhibited significantly slower release rate for formulation B. This is in accordance with In Vivo results where a moderate depression and retardation of plasma paracetamol concentrations for formulation B in comparison to form A was observed in each individual. This rendered the disposition rate constant significantly smaller (p)0.037) what is expected if flip-flop model is assumed. However, inconsistently the area under the plasma concentration curve was significantly larger for formulation B when compared to formulation A (p=0,026). This findings and the fact that the ratio unchanged paracetamol/metabolites in urine remained unchanged for the two types of suppository offered the hypothesis that the retardation of drug release from suppository leads to the increase of extent of absorption probably over the liver bypass mechanism.(Abstract truncated at 2000 characters).
Descriptors		ACETAMINOPHEN SUPPOSITORIES DRUG DELIVERY SYSTEMS