PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 7381708

Novel deconvolution method for linear pharmacokinetic systems with polyexponential impulse response.

P V Pedersen
View original source ↗Export metadata ↓

Abstract

A novel least-squares deconvolution method for estimating the rate and the extent of drug input into the systemic circulation is presented. The method is based on a polyexponential approximation of the impulse response and a polynomial approximation of the input rate. The method, which is readily implemented on a computer using any multiple linear regression program with a zero-intercept option, is compared to two other deconvolution methods using simulated data with various degrees of random noise added. It appears to have several significant advantages. The method is applied to plasma pentobarbital level data from oral and intravenous administration. The assumptions and limitations of deconvolution methods for analyzing drug input into the blood are discussed.

Explore related subjects

AbsorptionHumansKineticsMathematicsPentobarbitalPharmaceutical PreparationsTime FactorsJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

P V Pedersen. 1980. Novel deconvolution method for linear pharmacokinetic systems with polyexponential impulse response.. https://doi.org/10.1002/jps.2600690316

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1997

Sorption/desorption of radioactive contaminants by sediment from the Kara Sea.

To understand the long term impact of the disposal of radioactive waste on the Kara Sea, partition coefficients (Kd) for several important radionuclides, the mineralogy of the sediment, and the relationship of Kd to liquid-to-solid ratio were quantified. Sediment was obtained from four locations in the Kara Sea area. Slow sorption kinetics were observed for 85Sr, 232U, 125I and 99Tc, whilst sorption was rapid (less than 50 h to steady-state) for 137Cs, 210Pb, and 241Am. Partition coefficients (Kd) were determined using batch type experiments and sorption isotherms which were developed for 85Sr, 99Tc, 125I, U and 137Cs. Partition coefficients for 137Cs were approx. 350 ml/g for sediment from the Trough and 180 ml/g for Stepovogo Fjord. This difference may be caused by the lower fraction of expandable clay in sediment from the fjord. Uptake of 85Sr, 99Tc, 125I, and U were all similar for both locations, with Kd values averaging 4, 3, 17 and 60 ml/g, respectively. The Kd for 137 Cs varied non-linearly from 40 to 3800 ml/g as the liquid-to-solid ratio varied from 3.4 to 6500, but only when the sorption capacity was high compared to the mass of 137Cs in the closed system of the experiment. Under identical conditions, sediment with lower Kd values showed no effect. Oxidation of sediment effectively desorbed 99Tc from the solid phase, whilst it caused increased uptake of 85Sr and U. In sequential rinses with fresh seawater, desorption was limited to 60% of 137Cs and 85Sr, and 35% of uranium.

Absorption↗
PubMed1997

Steroidal glycoside cholesterol absorption inhibitors.

We have explored the use of steroidal glycosides as cholesterol absorption inhibitors which act through an unknown mechanism. The lead for this program was tigogenin cellobioside (1, tiqueside) which is a weak inhibitor (ED50 = 60 mg/kg) as measured in an acute hamster cholesterol absorption assay. Modification of the steroid portion of the molecule led to the discovery of 11-ketotigogenin cellobioside (5, pamaqueside) which has an ED50 of 2 mg/kg. Replacement of the cellobiose with other sugars failed to provide more potent analogs. However, large improvements in potency were realized through modification of the hydroxyl groups on the cellobiose. This strategy ultimately led to the 4", 6"-bis[(2-fluorophenyl)carbamoyl]-beta-D-cellobiosyl derivative of 11-ketotigogenin (51) with an ED50 of 0.025 mg/kg in the hamster assay, as well as the corresponding hecogenin analog 64 (ED50 = 0.07 mg/kg).

Absorption↗