Busulfan bioavailability.

M Hassan; P Ljungman; P Bolme; O Ringdén; Z Syrůcková; A Békàssy; J Starý; I Wallin; N Kållberg

Home/Archive/PubMed

PubMed · 7919328

Busulfan bioavailability.

M Hassan·P Ljungman·P Bolme·O Ringdén·Z Syrůcková·A Békàssy·J Starý·I Wallin·N Kållberg

View original source ↗Export metadata ↓

Abstract

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.

Explore related subjects

Administration, Oral Adult Age Factors Biological Availability Busulfan Child, Preschool Female Humans Infant Injections, Intravenous Male Metabolic Clearance Rate Middle Aged Journal Article Research Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

M Hassan, P Ljungman, P Bolme, O Ringdén, Z Syrůcková, A Békàssy, J Starý, I Wallin, N Kållberg. 1994-10-01. Busulfan bioavailability.. https://pubmed.ncbi.nlm.nih.gov/7919328/

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

KEEP EXPLORING

Related citations

PubMed2001

Memory deficits in adult rats following postnatal iron administration.

Two experiments investigated the effects of Fe(2+), administered postnatally to rat pups on days 10-12, upon tests of memory performance and motor behaviour. In experiment I, Wistar rat pups were administered Fe(2+) at doses of either 2.5, 7.5, 15.0 or 30.0 mg/kg, or vehicle, postnatally, and tested in the open-field at 3 months of age, followed 6 weeks later by testing in the radial arm maze. In the open-field test, only the 30.0 mg/kg Fe(2+) group showed a significantly decreased number of ambulations, but not rearings. In the radial arm maze, all four dose groups, demonstrated deficits in acquisition performance from test days 3 to 5. Retention quotients confirmed the cognitive deficits over all four Fe(2+) groups. In experiment II, rats were administered either 2.5, 7.5 or 22.5 mg Fe(2+) per kg, or vehicle, postnatally, and tested in the inhibitory avoidance (IA) conditioning and retention test at 3 months of age. In the IA conditioning test, groups were either given five 10-min preexposures to the test chamber (preexposed) or simply moved to another cage (non-preexposed). IA retention was blocked in non-preexposed rats administered 7.5 and 22.5 mg Fe(2+) per kg whereas in preexposed rats the 7.5 mg/kg group did not differ from the control (vehicle) group, although the preexposed control group showed significantly better retention than the non-preexposed control group. Postnatal iron administration appears to induce long-lasting detrimental effects upon performance of both appetitively and negatively reinforced tests of memory. Analysis of iron content indicated significant increases in the substantia nigra of the 7.5, 15.0 and 30.0 mg/kg dose groups, but not in the 2.5 mg/kg dose group. Postnatal iron administration appears to induce far-reaching effects upon the performance of certain learned behaviours.

Administration, Oral↗

PubMed2001

Re-evaluation of ivermectin efficacy against equine gastrointestinal parasites.

Two trials were conducted to confirm the efficacy of ivermectin paste against endoparasites of horses. In these trials, 20 ponies were treated with ivermectin oral paste at 200 mcg x kg body weight once on Day 0, and 20 ponies served as unmedicated controls. The animals carried naturally acquired parasite infections as confirmed by pretrial fecal examination. The animals were necropsied for worm recovery on Days 14, 15 or 16. Parasites recovered were identified to species. Horses treated with ivermectin had significantly (P<0.05) fewer (>99.0% reduction) adult small strongyles (Coronocyclus spp including C. coronatus, C. labiatus, C. labratus; Cyathostomum spp including C. catinatum, C. pateratum; Cylicocyclus spp including C. ashworthi, C. elongatus, C. insigne, C. leptostomum, C. nassatus, C. radiatus; Cylicodontophorus bicoronatus; Cylicostephanus spp including C. asymetricus, C. bidentatus, C. calicatus, C. goldi, C. longibursatus, C. minutus; Gyalocephalus capitatus; Parapoteriostomum spp including P. euproctus, P. mettami; Petrovinema poculatum; Poteriostomum spp including P. imparidentatum, P. ratzii) and adult large strongyles (Strongylus edentatus, S. vulgaris; Triodontophorus spp including T. brevicauda, T. serratus; Craterostomum acuticaudatum) than the controls. Ivermectin was also highly effective (94% to >99%, P<0.05-0.01) against Gasterophilus intestinalis larvae, Habronema spp., Oxyuris equi, Parascaris equorum. The data from these two trials confirm that ivermectin paste administered to horses orally at 200mcg x kg(-1) continues to be highly effective for treatment and control of a broad range of small and large strongyle species as well as other species of gastrointestinal parasites.

Administration, Oral↗

PubMed2001

In vivo evaluation of hydrochlorothiazide liquisolid tablets in beagle dogs.

This study was carried out to evaluate the absorption characteristics of experimentally developed hydrochlorothiazide liquisolid tablets using six male beagle dogs. Comparison with reference commercial tablets was made. As no bibliographic data were found for the pharmacokinetic parameters of the drug in dogs, an intravenous drug administration was included in the study. The drug was administered orally as a single 25 mg dose of commercial and liquisolid tablets on two occasions in a randomized two-way crossover design. The pharmacokinetic parameters of the drug post intravenous dosing were reported for the first time. The results of the oral administration revealed statistically significant differences between the liquisolid and the commercial tablets in the area under the plasma concentration-time curve, the peak plasma concentration, and the absolute bioavailability. On the other hand, no significant differences were observed between the two formulations with regard to the mean residence time, the mean absorption time, and the rate of absorption. The absolute bioavailability of the drug from the liquisolid tablets was 15% higher than that from the commercial one. The parametric 90% confidence intervals for the different parameters were higher than the commonly expected intervals for bioequivalency, indicating greater bioavailability of the liquisolid tablets.

Administration, Oral↗