Kinetic-dynamic modeling of lymphocytopenia induced by the combined action of dexamethasone and hydrocortisone in humans, after inhalation and intravenous administration of dexamethasone.

Ten healthy male volunteers received 5 mg of dexamethasone sodium phosphate (DEX) i.v. and, on an other occasion, by way of nebulization. Plasma DEX and hydrocortisone (HC) concentrations as well as blood lymphocyte count (BLC) were monitored over 12 hr and at 24 to 28 hr after DEX administration. Bioavailability of DEX after inhalation was about 27% of DEX i.v. DEX-induced depletion of plasma HC could be predicted with a pharmacokinetic model. The reonset rate of HC-production was dependent of DEX dose. BLCs declined after DEX administration, reaching a minimum between 4- and 8-hr postdosing. The DEX- and HC-induced depression of BLC could be described by an integrated pharmacokinetic-pharmacodynamic competitive-interaction model that assumes that both agonists act on the same receptor. With this model the potency and efficacy of DEX and HC with respect to lymphocytopenia could be estimated simultaneously. The potency of DEX was 10 times greater than the potency of HC. The estimated efficacy suggests that HC is only a partial agonist; the maximal lymphocytopenic effect (Emax) of HC was estimated at 80% (27-99%) of the efficacy of DEX. Our results indicate that DEX should be preferred instead of HC in conditions in which the lymphocytopenic effect is the primary systemic corticosteroid treatment goal.

Prophylaxis in gynaecological surgery: a prospective randomized comparison between single dose prophylaxis with amoxycillin/clavulanate and the combination of cefuroxime and metronidazole.

A prospective randomized comparison of a single pre-operative dose of 2.2 g amoxycillin/clavulanate versus the combination of 1.5 g cefuroxime plus 0.5 g metronidazole was conducted in 467 women, who underwent gynaecological surgery. The incidence of febrile morbidity, urinary tract infection, wound infection and the use of post-operative antimicrobial agents was similar in the two groups. Amoxycillin/clavulanate is as effective as a combination of cefuroxime and metronidazole and less expensive.

Penetration into lung tissue after intravenous administration of amoxycillin/clavulanate.

In order to investigate the penetration of amoxycillin and clavulanate into lung tissue, ten patients with a malignancy requiring a pulmonary resection, receiving 2000 mg amoxycillin and 200 mg clavulanate by intravenous injection, were studied. Samples of whole blood were taken before dosing and at the time of tissue removal. One to five grams of healthy lung tissue was taken from a segment or lobe other than that in which the tumour was located. All serum and tissue samples were analysed by a microbiological assay. The mean period to elapse before serum sample collection was 41.8 min at which time the mean concentrations were amoxycillin 71.3 and clavulanate 7.8 mg/l. The mean period to elapse before tissue collection was 54.3 min at which time the mean concentrations were amoxycillin 34.1 and clavulanate 2.3 mg/kg. These levels of amoxycillin and clavulanate are high enough to inhibit important pathogens in the lower respiratory tract.