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Biomedical subjects

A Finn

Publications and source records attributed to A Finn.

105 records · Page 6Linked to original sources
PubMed1980

Lipophilic drugs and lipoproteins: partitioning effects on chloroethylnitrosourea reaction rates in serum.

Chloroethylnitrosoureas are anticancer agents that undergo chemical reactions in vitro and in vivo to form active alkylating agents. The rate at which lipophilic chloroethylnitrosourease decompose in serum is faster than in aqueous solution and comparable to in vivo clearance rates. The increase in reaction rate is known to be caused by a reaction catalyzed by protein. Addition of lipoproteins to serum stabilizes chloroethylnitrosoureas to degradation. A model is presented that correlates serum decomposition rates to lipoprotein concentrations. This model involves partitioning of lipophilic chloroethylnitrosoureas into the hydrophobic core region of the lipoproteins where the chloroethylnitrosourea is chemically stable and is not free to undergo protein binding nor aqueous chemical degradation reactions. Normal interindividual variations of serum lipoprotein concentrations and hence partitioning may be a significant factor affecting the tissue distribution and pharmacokinetics of lipophilic drugs.

Carmustine↗
PubMed1979

The effect of phenobarbital pretreatment on the antitumor activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl-1-nitrosourea (PCNU), and on the plasma pharmacokinetics and biotransformation of BCNU.

Many patients being treated for primary and secondary brain tumors receive phenobarbital as an anticonvulsant. The effects of chronic oral administration of phenobarbital on the antitumor activity of BCNU, CCNU and PCNU against the intracerebral 9L tumor in rats were determined. Phenobarbital pretreatment eliminated the antitumor activity of BCNU and reduced the activity of PCNU and CCNU. Pretreatment with phenytoin, sodium methylprednisolone succinate and dexamethasone had little or no effect. Pharmacokinetic data for i.v. BCNU in the plasma of rats showed an increase in drug clearance for phenobarbital pretreated animals, compared to a control group. Larger differences were observed when BCNU was given i.p. The half-life of BCNU in sera from pretreated and control group rats was similar. Finally, the in vitro rate of BCNU disappearance in 9000 X g supernatants and microsomes from the livers of pretreated rats was 5-fold faster than the rate of disappearance of BCNU in supernatants from normal animals. We conclude that the chronic oral administration of phenobarbital induces a change in liver enzymes, which accelerates the clearance of BCNU, thereby reducing the antitumor activity of BCNU and the other nitrosoureas. Phenobarbital pretreatment reduces systemic BCNU toxicity.

Alkylating Agents↗
PubMed1976

Dehydroepiandrosterone sulfate loading test in the diagnosis of complicated pregnancies.

To assess placental and fetoplacental function, 50 mg of dehydroepiandrosterone sulfate was administered intravenously to 11 normal obstetric patients at 35 to 40 weeks and to 36 high-risk patients at 35 to 43 weeks of pregnancy. Plasma estradiol converted from dehydroepiandrosterone sulfate by the placenta increased in all patients after infusion, with maximal concentrations of 28 to 65 ng per milliliter 30 to 60 minutes after infusion (P less than 0.01). Plasma estetrol, produced by the fetus from estradiol, increased in all patients with maximal concentrations of 0.8 to 3.2 ng per milliliter four hours after infusion (P less than 0.01). In complicated pregnancies a subnormal rise of estradiol and estetrol was highly suggestive of fetal distress whereas a normal rise was associated with no fetal distress. The simultaneous determination of estradiol and estetrol after dehydroepiandrosterone sulfate infusion may reflect placental and fetoplacental function, and may be used as an adjunct to other methods of assessing fetal well-being.

Birth Weight↗
PubMedDate not supplied

Effect of dose and food on the bioavailability of cefuroxime axetil.

Cefuroxime axetil is an ester pro-drug which permits the oral administration of cefuroxime. This study was designed to evaluate the dose proportionality of four different doses administered after a meal and to determine the absolute bioavailability of cefuroxime axetil administered with and without food. The study was a six-way randomized crossover trial in 12 normal male volunteers. Subjects received an intravenous dose of cefuroxime (500 mg) and five oral doses of cefuroxime axetil (125, 250, 500-twice, 1000 mg). The intravenous dose and one of the 500 mg doses was administered after an overnight fast. The other four oral doses were administered after a standard meal. Blood samples were collected prior to each dose and serially for 12 h after the dose. Urine was collected for 24 h. Plasma and urine samples were analysed for cefuroxime by high pressure liquid chromatography. There was a linear relationship between the fed dose and both the area under the plasma concentration time curve (r2 = 0.958) and the peak plasma concentration (r2 = 0.943). Based on a comparison of the AUC for the oral and intravenous data, 36 per cent of the fasting and 52 per cent of the fed 500 mg doses were absorbed. The mean peak plasma concentration was 43 per cent greater after the fed dose than the fasting dose. A plot of the mean fraction of unabsorbed drug versus time reveals that absorption is an apparent zero order process from 0.5 to 3 h after dosing.

Adult↗
PubMedDate not supplied

Chemokine receptors and their role in vascular biology.

Chemokines play an important role in the process of leukocyte recruitment and activation at sites of inflammation. Until recently, the actions of chemokines and the expression of their receptors have only been described on different leukocyte populations. However, increasing evidence has suggested that non-haematopoietic cell types are capable of binding and responding to a number of chemokines. The functional expression of certain chemokine receptors has recently been described on vascular endothelial and smooth muscle cells. These findings provide new insight into the activities of chemokines and indicate that these molecules have a more widespread cellular target than first envisaged. Studies carried out to date indicate that chemokines and their respective receptors play an important role in the regulation of angiogenesis and angiostasis. They may also be involved in developmental and pathological processes such as organ vascularization, embryogenesis and arteriosclerosis.

Blood Vessels↗