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Biomedical subjects

I Wallin

Publications and source records attributed to I Wallin.

At least 19 recordsLinked to original sources
PubMed1999

Stability of 5-aminolevulinic acid in aqueous solution.

The chemical stability of 5-aminolevulinic acid (ALA) was studied in aqueous solution as a function of concentration, pH, temperature and in the presence of ethylenediaminetetraacetic acid (EDTA). The degradation of ALA was followed by reversed-phase liquid chromatography using a pH where ALA is protonated (pKa1=3.90; pKa2=8. 05, as determined potentiometrically). ALA was degraded by a reaction following second order kinetics. Stock solutions of 1% (60 mM) ALA were incubated at 50 degrees C. At pH 2.35, ALA was stable during the whole incubation period (37 days). The half-lives for the second-order decomposition of 1% ALA at pH 4.81 and 7.42 were 257 and 3.0 h, respectively. The degradation rate increased about 1.5 times with each 10 degrees C rise in temperature at pH 7.53 within the range studied (37-85 degrees C). The energy of activation, Ea, for the second-order decomposition of ALA was 43.7 kJmol-1. EDTA did not influence the degradation of ALA when a mixture of 1% ALA and 1% EDTA was incubated at pH 7.42.

Aminolevulinic Acid↗
PubMed1997

Risk factors for cardiovascular disease during the period 1985-1995 in Göteborg, Sweden. The GOT-MONICA Project.

AIMS: To report levels of cardiovascular risk factors in 1985, 1990 and 1995 in three population samples in Göteborg, Sweden, and to compare with previous population risk factor levels. POPULATION: The study was performed within the framework of the WHO MONICA Project which compares risk factor levels as well as the incidence of coronary heart disease and stroke in 38 populations. METHODS: Three random samples of men and women aged 25-34, 35-44, 45-54 and 55-64 comprising 152-218 subjects in each age group who responded to the invitation for screening procedures which included questionnaires, physical and laboratory investigations in 1985, 1990 and 1995. RESULTS: More men than women had smoked, except for those aged 35-44 where there was no difference between men and women. The proportion of men who had smoked decreased strongly between the first and third investigations (P < 0.0001), particularly amongst the younger age-groups, with a similar tendency amongst women. In the 25-44-years age group there was a tendency towards more women than men to be smokers in 1995. Snuff was used by 27% and 19% of men aged 25-34 and 35-44 years, respectively, in 1995. Up to 5% of women used snuff; higher in the younger age groups. More young men than women reported regular physical activity during leisure time with a tendency towards an increase from 1985 to 1995. The proportion of men reporting psychological stress varied little over the study period, but women aged 25-34 reported increased stress from 1985 to 1995. Body weight increased whereas height remained stable and consequently body mass index increased in men and women (P = 0.0001). Similarly, waist:hip ratio (measured in 1990 and 1995 only) also increased (P = 0.0001). Mean systolic and diastolic blood pressure increased with age and there was also a small increase between 1985 and 1995. Systolic blood pressure increased by a mean of 1.24 mmHg per 5-year period independent of sex and age (P = 0.0001). Antihypertensive treatment increased with age, but was stable between 1985 and 1995. Serum total and LDL cholesterol concentrations increased with age, and there was a nonsignificant tendency also to higher HDL cholesterol concentrations at older ages. Serum total cholesterol concentration declined between 1985 and 1995, and HDL cholesterol declined significantly between 1985 and 1995 in all age groups for men and women only when all age groups were analysed together. Similar to total cholesterol, levels of LDL cholesterol declined between 1985 and 1995 for all ages. Serum triglyceride levels increased for men and women between 1985 and 1995.

Adult↗
PubMed1994

Busulfan bioavailability.

Busulfan is widely used as a component of the myeloablative therapy in bone marrow transplantation. Recent studies have shown that the drug disposition is altered in children and is associated with less therapeutic effectiveness, lower toxicities, and higher rates of engraftment failure. We have evaluated the bioavailability of the drug in two groups of patients: eight children between 1.5 and 6 years of age and eight older children and adults between 13 and 60 years. Oral bioavailability showed a large interindividual variation. In children, the bioavailability ranged from 0.22 to 1.20, and for adults, it was within the range 0.47 to 1.03. The elimination half-life after intravenous administration in children (2.46 +/- 0.27 hours; mean +/- SD) did not differ from that obtained for adults (2.61 +/- 0.62 hours). However, busulfan clearance normalized to body weight was significantly higher in children (3.62 +/- 0.78 mL.min-1.kg-1) than that in adults (2.49 +/- 0.52 mL.min-1.kg-1). Also, the distribution volume normalized for body weight was significantly higher in children (0.74 +/- 0.10 L.kg-1) compared with 0.56 +/- 0.10 L. kg-1 in adults. The difference in clearance between children and adults was not statistically significant when normalized to body surface area, which most probably shows that busulfan dosage should be calculated on the basis of surface area rather than body weight. However, to avoid drug-related toxicities, drug monitoring and an individual dose adjustment should be considered because of the variability in busulfan bioavailability.

Administration, Oral↗
PubMed1994

Food-induced increase in bioavailability of 5-methoxypsoralen.

5-Methoxypsoralen (5-MOP) in combination with ultraviolet light exposure is used for the treatment of psoriasis. The effect of food on the pharmacokinetics of 5-MOP was evaluated in a randomized, crossover study in nine healthy subjects. Each subject received the tablets with a standardized breakfast or under fasting conditions. The food had a dramatic effect on the bioavailability of 5-MOP. Five of the subjects showed no measurable quantities (detection limit of the analytical technique 1 ng.ml-1) of 5-MOP when the drug was given under fasting conditions. However, plasma peak concentration within the range 37-144 ng.ml-1 (median 102 ng.ml-1) was measured when the drug was taken with food. The time for the plasma peak concentration was within the range 2.0-5.1 h (median 3.0 h) under non-fasting conditions. The elimination half-life was within the range 1.4-2.7 h (median 1.9 h). We conclude that it is imperative that 5-MOP tablets are administered together with food.

5-Methoxypsoralen↗
PubMed1993

Pharmacokinetics of peptichemio in myeloma patients: release of m-L-sarcolysin in vivo and in vitro.

Peptichemio (PTC) is a mixture of six synthetic oligopeptides, each of which contains the alkylating residue m-[di(2-chloroethyl)amino]-L-phenylalanine (L-mSL). The fate of PTC was investigated in eight patients with multiple myeloma after intravenous infusion of the drug. The quantitative analysis of the plasma samples was performed by liquid chromatography with fluorometric detection. L-mSL was rapidly released from the peptides and reached its maximal plasma concentration at the end of the infusion. Its median elimination half-life was 1.73 (range, 0.72-2.41) h. It was possible to follow the concentration of only one of the peptides, L-mSL-L-Arg(NO2)-L-Nval.OEt, during and shortly after the infusion of PTC. The stability of L-mSL and the peptides was studied in buffer solution (pH 7.3), plasma, and blood. The stability of some of the peptides was drastically decreased in blood, the degradation half-lives being only about 1 min. We conclude that L-mSL plays an important role in the mechanism of action of PTC.

Aged↗
PubMed1993

Influence of prophylactic anticonvulsant therapy on high-dose busulphan kinetics.

The pharmacokinetics of high-dose busulphan was studied in 17 patients during conditioning prior to bone marrow transplantation using deuterium-labeled busulphan (d8-BU). About 50% of busulphan doses 1 and 16 was replaced with d8-BU. Patients were treated with phenytoin or diazepam as prophylactic anticonvulsant therapy. Patients who received phenytoin demonstrated significantly higher clearance (mean +/- SD, 3.32 +/- 0.99 ml min-1 kg-1), a lower area under the concentration-time curve (AUC, 5,412 +/- 1,534 ng h ml-1; corrected for dose/kilogram) and a shorter elimination half-life (3.03 +/- 0.57 h) for the last dose of d8-BU (dose 16) as compared with the first dose (2.80 +/- 0.78 ml min-1 kg-1, 6,475 +/- 2,223 ng h ml-1 and 3.94 +/- 1.10 h, respectively). No difference in the above mentioned pharmacokinetic parameters was seen in patients treated with diazepam. Moreover, a continuous decrease in the steady-state level of busulphan was observed in four of seven patients in the phenytoin-treated group, whereas in the diazepam group, such a decrease was seen in only one of eight patients. We conclude that phenytoin used as prophylactic anticonvulsant therapy alters busulphan pharmacokinetics and, most probably, its pharmacodynamics. For adequate prophylactic therapy, anticonvulsants with fewer enzyme-inductive properties than phenytoin should be used.

Adult↗
PubMed1991

Pharmacokinetics of high-dose busulphan in relation to age and chronopharmacology.

Busulphan levels in plasma were measured in 27 patients during conditioning therapy (1 mg/kg x 4 for 4 days) before bone marrow transplantation. The mean minimal concentration found in children aged less than 5 years (237 ng ml-1) was lower than that observed in adults or older children (607 and 573 ng ml-1, respectively). The AUC for the last dose was significantly lower in young children (2.315 h ng ml-1) than in adults or older children (6,134 and 5,937 h ng ml-1, respectively). The elimination half-life for the last dose in young children was shorter (2.05 h) than that in either adults (2.59 h) or older children (2.79 h). When the AUC was normalized for body surface area, the difference between young children and the other groups was smaller but remained statistically significant. The total body clearance was significantly higher in young children (7.3 ml min-1 kg-1) as compared with both older children and adults (3.02 and 2.7 ml min-1 kg-1, respectively). The plasma levels of busulphan showed circadian rhythmicity, especially in young children. The concentration measured during the night in some patients was up to 3-fold that observed during daytime. We conclude that the busulphan dosage for children must be reconsidered and that further studies are urgently needed to develop an optimal therapy.

Adolescent↗
PubMed1990

Oral melphalan pharmacokinetics: influence of interferon-induced fever.

The influence of interferon-induced fever on oral melphalan pharmacokinetics has been studied in 10 myeloma patients in a randomized crossover design. The melphalan dose (0.25 mg/kg) was given alone and 5 hours after the administration of human interferon alpha (7 x 10(6) IU/m2), respectively. The plasma concentration of melphalan was determined by liquid chromatography with fluorometric detection after derivatization of melphalan with N-acetylcysteine. The area under the plasma concentration-time curve (AUC) was significantly lower (p = 0.02) when melphalan was given with interferon. There was a significant negative correlation (p = 0.008) between body temperature and dose normalized AUC, whereas no effect was noticed on the maximum plasma concentration (Cmax) and on the time to obtain Cmax. The rate of elimination showed a tendency (p = 0.06) to increase with increasing body temperature. It is suggested that the cytotoxicity of the drug is most probably enhanced because of the higher alkylating activity of the compound at elevated body temperatures.

Aged↗
PubMed1989

Pharmacokinetic and metabolic studies of high-dose busulphan in adults.

The pharmacokinetics of high-dose busulphan was studied in adult patients with acute myeloblastic leukaemia after oral doses of 1 mg.kg-1 every 6 h for 4 days. The mean steady-state plasma concentration was 1080 ng/ml-1 during the treatment. Individual steady-state concentrations after the last dose on average were 32% lower than those predicted from total AUC measurements following the first dose. Mean elimination half-life in plasma was 2.3 h after the last dose and 3.4 h after the first dose which suggests that busulfan may increase its own metabolic rate on repeated treatment. The cerebrospinal fluid/plasma concentration ratio of busulphan was 1.3. Busulphan showed insignificant protein binding in plasma (7.4%). About 2% of the dose was excreted unchanged in the urine. For the first time sulpholane, 3-hydroxysulpholane and tetrahydrothiophene 1-oxide were identified as urinary metabolites of busulphan in man.

Adult↗
PubMed1989

Pharmacokinetics of oral melphalan in relation to renal function in multiple myeloma patients.

The impact of renal function on oral melphalan pharmacokinetics was studied in 15 patients with multiple myeloma. A two-fold interindividual variation in the plasma concentration-time curve (AUC) was found. An increase in AUC and melphalan mean residence time (MRT) was noted in patients with renal dysfunction. No correlation was found between GFR and the terminal plasma half-life time. We conclude from these results that renal dysfunction is associated with an increase in AUC and MRT of oral melphalan. A careful follow-up of hematological toxicity and possibly a dose reduction of melphalan are proposed for myeloma patients with renal impairment.

Aged↗
PubMed1989

Cerebrospinal fluid and plasma concentrations of busulfan during high-dose therapy.

A patient with acute myeloblastic leukemia received high-dose busulfan (1 mg/kg by mouth every 6 h for 4 days) as myelo-ablative therapy for autologous bone marrow transplantation. Rapid entry of busulfan into the cerebrospinal fluid (CSF) was observed. Plasma and CSF concentrations of busulfan were comparable during the 4 days of treatment. The elimination half-lives of busulfan in plasma and CSF were 2.6 h and 2.8 h respectively during the first 12 h after the last dose.

Bone Marrow Transplantation↗
PubMed1988

Inter- and intraindividual differences in oral chlorambucil pharmacokinetics.

Inter- and intraindividual variation in the pharmacokinetics of oral chlorambucil was investigated in patients with chronic lymphocytic leukaemia. Five patients were given in randomized order 15, 40, 60 and 70 mg chlorambucil p.o. and plasma was analyzed for chlorambucil and its cytotoxic metabolite phenyl acetic acid mustard. The area under the plasma concentration-time curve of chlorambucil varied two- to fourfold between patients at each dose level. The AUC of the metabolite was higher and showed twofold interindividual variation. The intraindividual dose-corrected AUCcs also varied twofold. No dose dependency of the dose corrected AUC was seen either for chlorambucil or the metabolite. Elimination of both compounds form plasma was rapid, with half-lives of 1.01 and 1.94, respectively.

Administration, Oral↗
PubMed1988

Concentration and time-dependent inter-relationships for cytotoxicities of nitrogen mustard drugs against lymphoblasts in-vitro.

Peripheral lymphoblasts were exposed either to different initial concentrations of the alkylating agents (melphalan, chlorambucil or phenylacetic acid mustard) using a fixed incubation time or a constant [3H]methylthymidine incorporation into the trichloracetic acid-insoluble fraction of the cells. The concentration-time relationships were evaluated by calculating the amount of drug which had chemically reacted in the incubation system. Melphalan showed lower cytotoxicity at short exposure times and high drug concentrations, while chlorambucil exhibited higher cytotoxicity at longer exposure times. In the latter case the effect could be accounted for by the cytotoxic activity of monohydroxy chlorambucil which was formed in the incubation system.

Cell Survival↗
PubMed1988

Concentration of trimethylpsoralen in blood and skin after oral administration.

Trimethylpsoralen (TMP) concentrations were determined in blood and skin of 21 patients given oral TMP therapy and were compared to data obtained from 5 patients treated with TMP baths. The quantitative determination was performed by gas chromatography with selected ion monitoring. Concentrations of up to 5.6 ng/ml were detected in whole blood from orally TMP treated patients, with about the same concentrations in patients given TMP baths. Whole skin biopsies from patients ingesting TMP showed concentrations in 14 patients that ranged from 30 to 1250 ng/g skin, median value 85 ng/g. Large interindividual variations were observed. Stripped skin from 5 patients after TMP baths showed a somewhat higher median value of 160 ng/g and their entire skin had fairly high concentrations, with a median value of 390 ng/g, probably mostly bound to stratum corneum. Different concentrations in different parts of the skin may explain the difference in phototoxic capacity when the drug is given locally.

Administration, Oral↗
PubMed1984

Effect of food on pharmacokinetics of chlorambucil and its main metabolite, phenylacetic acid mustard.

The influence of food intake on the pharmacokinetics of chlorambucil (C) and its cytotoxic metabolite, phenylacetic acid mustard (PAM), has been studied in man after oral doses of chlorambucil. The administration of chlorambucil with food resulted in slower absorption than when fasting. However, the area under the plasma concentration-time curve (AUC) was unaffected. The mean ratio AUCPAM/AUCC was 2.8 (range 1.4-7.1) under fasting and 3.3 (range 1.3-7.4) under nonfasting conditions. The metabolite very probably plays an important role in the cytotoxic effects observed after administration of C, since calculations show that a major fraction of the metabolite is eliminated by alkylation reactions.

Adult↗
PubMed1983

Pharmacokinetics of chlorambucil in man after administration of the free drug and its prednisolone ester (prednimustine, Leo 1031).

The pharmacokinetics of chlorambucil has been investigated in a cross over study after oral administration of the free drug (10 mg) and its prednisolone ester (prednimustine, 100 mg). The bioavailability of chlorambucil was about five times lower when given as prednimustine as compared to administration of the free drug. The peak plasma concentration was about twice as high and it was obtained more rapidly when the free drug was given. No intact prednimustine could be detected in plasma.

Aged↗