Busulfan is a small, highly lipophilic molecule that easily crosses the blood brain barrier. Following absorption, 32% and 47% of busulfan are bound to plasma proteins and red blood cells, respectively. 

Busulfan absorption from the gastrointestinal tract is essentially complete. This has been demonstrated in radioactive studies after both intravenous and oral administration of 35S-busulfan, 14C-busulfan, and 3H-busulfan. Following intravenous administration of a single therapeutic dose of 35S-busulfan, there was rapid disappearance of radioactivity from the blood and 90% to 95% of the 35S-label disappeared within 3 to 5 minutes after injection. After either oral or intravenous administration of 35S-busulfan, 45% to 60% of the radioactivity was recovered in the urine in the 48 hours after administration; the majority of the total urinary excretion occurring in the first 24 hours. Over 95% of the urinary 35S-label occurs as 35S-methanesulfonic acid. Oral and intravenous administration of 1,4-14C-busulfan showed the same rapid initial disappearance of plasma radioactivity as observed following the administration of 35S-labeled drug. Cumulative radioactivity in the urine after 48 hours was 25% to 30% of the administered dose (contrasting with 45% to 60% for 35S-busulfan), and suggests a slower excretion of the alkylating portion of the molecule and its metabolites than for the sulfonoxymethyl moieties.  
  
Regardless of the route of administration, 1,4-14C-busulfan yielded a complex mixture of at least 12 radiolabeled metabolites in urine; the main metabolite being 3-hydroxytetrahydrothiophene-1,1-dioxide.

Pharmacokinetic studies employing 3H-busulfan labeled on the tetramethylene chain confirmed a rapid initial clearance of the radioactivity from plasma, irrespective of whether the drug was given orally or intravenously. 

A study compared a 2-mg single IV bolus injection to a single oral dose of a 2-mg tablet of nonradioactive busulfan in 8 adult patients 13 to 60 years of age. The study demonstrated that the mean ± SD absolute bioavailability was 80% ± 20% in adults. However, the absolute bioavailability for 8 children 1.5 to 6 years of age was 68% ± 31%.

In another study of 2, 4, and 6 mg of busulfan, given as a single oral dose on consecutive days (starting with the lowest dose) in 5 adult patients, the mean dose-normalized (to 2 mg dose) area under the plasma concentration-time curve (AUC) was about 130 ng•hr/mL, while the mean intra- and inter-patient variability was about 16% and 21%, respectively. Busulfan was eliminated with a plasma terminal elimination half-life (t1/2) of about 2.6 hours, and demonstrated linear kinetics within the range of 2 to 6 mg for both the maximum plasma concentration (Cmax) and AUC. The mean Cmax for the 2-, 4-, and 6-mg doses (after dose normalization to 2 mg) was about 30 ng/mL. A recent study of 4 to 8 mg as single oral doses in 12 patients showed that the mean ± SD Cmax (after dose normalization to 4 mg) was 68.2 ± 24.4 ng/mL, occurring at about 0.9 hours and the mean ± SD AUC (after dose normalization to 4 mg) was 269 ± 62 ng•hr/mL. These results are consistent with previous results. In addition, the mean ± SD elimination half-life was 2.69 ± 0.49 hours. 

The elimination of busulfan appears to be independent of renal function. This probably reflects the extensive metabolism of the drug in the liver, since less than 2% of the administered dose is excreted in the urine unchanged within 24 hours. The drug is metabolized by enzymatic activity to at least 12 metabolites, among which tetrahydrothiophene, tetrahydrothiophene 12-oxide, sulfolane, and 3-hydroxysulfolane were identified. These metabolites do not have cytotoxic activity.

There is no experience with the use of dialysis in an attempt to modify the clinical toxicity of busulfan. One technical difficulty would derive from the extremely poor water solubility of busulfan.  
  
Additionally, all studies of the metabolism of busulfan employing radiolabeled materials indicate rapid chemical reactivity of the parent compound with prolonged retention of some of the metabolites (particularly the metabolites arising from the “alkylating” portion of the molecule). The effectiveness of dialysis at removing significant quantities of unreacted drug would be expected to be minimal in such a situation. Currently, there are no available data on the effect of food on busulfan bioavailability.