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An earlier whole-body autoradiographic study in mice revealed large differences between the tissue distribution of daunorubicin (D) after administration as free drug as as DNA-linked D. Therefore, the pharmacokinetics of D administered as free drug or linked to DNA was studied in 15 adult patients with acute non-lymphoblastic leukemia. The data obtained following infusion of free drug over either 45 or 240 min could be fitted to a two-compartment open-body model. With the D-DNA infusion considerably higher plasma concentrations were achieved, with a slower distribution and elimination from plasma than seen after the administration of free drug. this confirmed earlier animal data indicating a different pharmacokinetic behavior of D when it was administered linked to DNA. Furthermore, different pharmacokinetic parameters were obtained for D during infusion and in the post-infusion phase after administration of DNA-linked D (P less than 0.005). This finding strongly indicates that the D-DNA acts as a slow-release preparation in humans, which might modify tissue distribution and toxic side-effects of the drug. [ABSTRACT FROM AUTHOR]

The stability of chlorambucil and its degradation product 4-[p-(2-chloroethyl-2-hydroxyethylamino)phenyl]butyric acid (I) was studied using reversed-phase high-pressure liquid chromatography. The degradation rate of chlorambucil was unaffected by pH between pH 5 and 10 but decreased at lower pH. The degradation rates of chlorambucil and I differed only slightly (pH < 6). The proteolytic properties of the compounds were studied using spectrophotometric and partition techniques.

Five healthy fasting male subjects were each given single doses of intravenous ampicillin (471 mg), oral ampicillin tablets (495 mg), oral bacampicillin hydrochloride tablets (562 mg ampicillin equivalent), and oral pivampicillin hydrochloride capsules (491) mg ampicillin equivalent) in a crossover experiment. The resulting concentrations of ampicillin were determined in plasma and urine. The pharmacokinetic analysis was made according to a two-compartment open model. The total distribution volume of unbound ampicillin during the disposition phase was 0.247 +/- 0.045 (SD) liter/kg, which is only slightly more than the extracellular fluid, suggesting that tissue binding and intracellular distribution of ampicillin are limited. The bioavailability of the esters bacampicillin (86 +/- 11%) and pivampicillin (92 +/- 18%) was significantly greater than that of ampicillin (62 +/- 17%); however, the difference between the esters was not statistically significant. The adsorption for all drugs given orally proceeded at a constant rate, suggesting zero-order release rates from the products. The adsorption rate was highest for bacampicillin (0.89 +/- 0.39 of dose absorbed per minute), followed by pivampicillin (0.64 +/- 0.19) and ampicillin (0.58 +/- 0.16). Bacampicillin also had the shortest lag time for the start of absorption (7.0 +/- 0.9 min) under the present conditions. Thus, in comparison with ampicillin, the esters have a higher bioavailability, which, in fact, is close to the theoretically highest possible value by clearance concepts. The higher bioavailability in connection with higher absorption rates may be clinically important in ampicillin treatment by the oral route.

A prevalence study of the antibiotic usage in the surgical departments at the Karolinska Hospital, Stockholm, showed that 126/517 hospitalized patients (24%) received antibiotics and that 100/306 operated patients (33%) received antibiotics. 44 (44%) of the operated patients were given their antibiotics as prophylaxis and 46 (37%) of all patients receiving antibiotics were given them as prophylaxis. Antibiotics were administered intravenously to 35 (28%) patients, orally to 75 (60%), and topically to 16 patients (13%) (eye department only). The most commonly used drugs in prophylaxis were isoxazolylpenicillins and trimethoprim-sulphonamide while cephalosporins accounted for a minor part. In therapy the most commonly used drug was isoxazolylpenicillin, followed by ampicillin derivatives, metronidazole, tetracyclines, trimethoprim-sulphonamide and cephalosporins. The pattern of antibiotic usage differed markedly between departments.

Intravesical instillation of Adriamycin has successfully been used in the treatment of bladder tumours. The Adriamycin concentration in the bladder has been monitored and the area under the bladder concentration-time curve, AUC, is proposed to be considered rather than the amount of instilled drug when optimizing the treatment schedules. pH effects which may arise in the bladder when instilling protolytic drugs like Adriamycin are discussed.

Kinetics of 8-methoxsalen were studied in 5 healthy subjects under fasting and nonfasting conditions. The plasma concentration-time data could be fitted to a zero order absorption one-compartment model. The area under the curve (AUC) values were higher (p less than 0.05) under nonfasting compared to fasting conditions, indicating higher relative bioavailability of the drug in the presence of food. No significant differences were observed in the lag-time for the start of the absorption, the apparent zero-order absorption rate constant, or the elimination rate constant. It is suggested that the drug should be taken in a standardized way in relation to food during the ultraviolet (UV) light treatment.