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  • 1
    Electronic Resource
    Electronic Resource
    Food-induced increase in bioavailability of 5-methoxypsoralen (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 375-377 
    Details
    ISSN: 1432-1041
    Keywords: 5-Methoxypsoralen ; Psoriasis ; food ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194409
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of chlorambucil in man after administration of the free drug and its prednisolone ester (prednimustine, Leo 1031) (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 251-253 
    Details
    ISSN: 1432-1041
    Keywords: chlorambucil ; prednimustine ; plasma concentrations ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613827
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  • 3
    Electronic Resource
    Electronic Resource
    Effect of food on pharmacokinetics of chlorambucil and its main metabolite, phenylacetic acid mustard (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 111-114 
    Details
    ISSN: 1432-1041
    Keywords: chlorambucil ; chronic lymphocytic leukaemia ; phenylacetic acid mustard ; food intake ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00553164
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of food on pharmacokinetics of chlorambucil and its main metabolite, phenylacetic acid mustard (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 111-114 
    Details
    ISSN: 1432-1041
    Keywords: chlorambucil ; chronic lymphocytic leukaemia ; phenylacetic acid mustard ; food intake ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02395216
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  • 5
    Electronic Resource
    Electronic Resource
    Inter- and intraindividual differences in oral chlorambucil pharmacokinetics (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 551-554 
    Details
    ISSN: 1432-1041
    Keywords: lymphocytic leukaemia ; chlorambucil ; phenylacetic acid mustard ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558252
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  • 6
    Electronic Resource
    Electronic Resource
    Pharmacokinetic and metabolic studies of high-dose busulphan in adults (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 525-530 
    Details
    ISSN: 1432-1041
    Keywords: busulphan ; leukaemia ; high-dose pharmacokinetics ; metabolism ; bone marrow transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558081
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  • 7
    Electronic Resource
    Electronic Resource
    Determination of 8-methoxypsoralen in plasma by electron capture gas chromatography
    Amsterdam : Elsevier
    Journal of Chromatography A 140 (1977), S. 157-164 
    Details
    ISSN: 0021-9673
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/S0021-9673(00)88408-3
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  • 8
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of high-dose busulphan in relation to age and chronopharmacology (1991)
    Springer
    Cancer chemotherapy and pharmacology 28 (1991), S. 130-134 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Busulphan levels in plasma were measured in 27 patients during conditioning therapy (1 mg/kg×4 for 4 days) before bone marrow transplantation. The mean minimal concentration found in children aged 〈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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689702
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