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Treatment with lornoxicam 4 mg twice daily for 14 d did not produce any change in salivary antipyrine elimination in 11 of 12 healthy volunteers. Anomalous results in one subject are presented and discussed.

Clinical phase I pharmacokinetic studies with lornoxicam were performed with the 4 mg dose of lornoxicam. Lornoxicam was administered as an aqueous solution both orally and intravenously to young, healthy, male volunteers. The total excretion of lornoxicam via urine and faeces after oral administration was determined by administering 14C-labelled compound. The results show that the parent compound and the main metabolite, 5'-hydroxy-lornoxicam, were found in plasma. However, in urine, no lornoxicam was detected, only 5'-hydroxy-lornoxicam. After oral as well as intravenous administration, a short terminal half-life of lornoxicam in the range of 4-5 hours was found. Given orally as solution, lornoxicam was rapidly and almost completely absorbed.

Lornoxicam is a new, highly potent antirheumatic agent which is an oxicam derivative. Although highly potent as a cyclo-oxygenase inhibitor, the compound does not cause inhibition of 5-lipoxygenase and does not appear to shunt arachidonic acid through this cascade. This powerful inhibition of cyclo-oxygenase has manifested itself as highly potent analgesic and anti-inflammatory effects in animal studies and also prevented the bone destruction which normally occurs in the adjuvant polyarthritic rat. To explain this finding, studies have demonstrated that lornoxicam inhibits polymorphonuclear (PMN)-leukocyte migration; inhibits the release of superoxide from human PMN-leukocytes; inhibits the release of platelet derived growth factor (PDGF) from human platelets and stimulates the synthesis of proteoglycans in cartilage in tissue culture. Lornoxicam is well absorbed and has a plasma t1/2 in man of 4 hours which is distinctly different from other oxicams. It is metabolized in animals and in man to the 5'-hydroxy-metabolite which is inactive in pharmacological tests. In vitro and in vivo animal safety studies have demonstrated both subchronically and chronically that lornoxicam manifests no unusual toxicity, is not a mutagen nor is it tumorigenic and causes no fetal teratogenicity in reproduction studies.

Ten patients with normal liver and kidney functions were admitted to a urology department for prostatectomy because of benign prostatic hypertrophy. They received a twice daily administration of 2 tablets of sulfametrole/trimethoprim (Lidaprim) for 4 days; the last dose of 2 tablets was given 4 hours before surgery. Having been enucleated by the suprapubic route, the prostatic glands were examined both histologically and chemico-analytically. The concentrations of the chemotherapeutically active substances were determined in the plasma and in the prostatic tissues. The prostatic tissue concentration of sulfametrole was 24,0 +/- 8,6 mg/kg and that of trimethoprim 7,1 +/- 2,2 mg/kg.

Lidaprim, a bactericidal chemotherapeutical agent, was administered to 10 patients in a children's hospital, in the form of an oval suspension for children. The initial dosage was given on an empty stomach, the second after a standard meal. The concentrations of the chemotherapeutical agents in the plasma and the urine were chemically analysed. The bio-availability of the preparation was very good. A standard meal, taken just before dosage, led to a delay in absorption both for Trimethoprim and Sulfametrol. In the period under surveillance, 0-12 hours after administration, an absorption loss could be calculated from the plasma and urine levels in the case of both Trimethoprim and Sulfametrol. In spite of this effect, adequate plasma and urine levels with a bactericidal action, were achieved with the usual dosage. The clinical success and compatibility of the preparation were good in every single case.

A report is given on the examination of the levels of sulfametrole and trimethoprim in blood and lung tissue of 29 patients with pulmonary tumours of various origin, who were subjected to a pre-operative treatment with 2 tablets 2 times daily of the sulfametrole-trimethoprim combination Lidaprim for an average period of one week because of concurrent bronchopulmonary infections. About 14 hours after the last tablet dose samples of tumour-free lung tissue and blood were removed during the operation and subjected to a chemical analysis of sulfametrole and trimethoprim. The mean blood level of sulfametrole was 30.3 micrograms/ml and of trimethoprim 2.0 micrograms/ml; the mean levels in the lung tissue was 19.2 micrograms/g of sulfametrole and 9.2 micrograms/g of trimethoprim. Trimethoprim via the blood is stored in the lung tissue. The relationship of these results to the good clinical activity of the combination sulfametrole/trimethoprim in the treatment of infections of bacterial origin in the upper and lower airways is discussed.

Pharmacokinetic parameters were determined after the oral administration of a single tablet containing 200 mg celiprolol HCl to 8 healthy volunteers with normal kidney function and 6 patients with stable impaired renal function of different degrees of severity. The plasma levels and the urinary excretion of celiprolol were followed up for 48 hours after administration with the help of specific chemo-analytical methods. The substance was equally well absorbed both by healthy volunteers and patients with renal disease. While the cumulative renal excretion (0 to 48 hours after administration) was reduced from 18.2% in healthy volunteers to 2.3% of the applied dose in kidney patients, the global elimination constant k fell from 0.104 h-1 in healthy volunteers to 0.072 h-1 in the patients with renal disease. It can be assumed that in patients with impaired renal function at least a part of the lacking renal elimination of celiprolol can be taken over by "extrarenal elimination". According to the method of Dettli a reduction in dosage of the beta 1-blocker, celiprolol is not necessary in patients with more or less impaired kidney function.

Studies on the influence of substances on the central nervous system and on the function of the blood-CSF-barrier made long-term cannulation of the CSF compartment interesting. This study was to test, whether a permanent CSF-drainage from any point of the subarachnoid space was possible with modified "tissue cages" (Guyton 1963). For that purpose a steel wire cage and a teflon cage were implanted subarachnoidally into beagle dogs. The two cages stopped draining on the second and on the third day respectively. Histological examination showed, that, because of the strong reaction of animal tissue to implanted material, direct cannulation of the CSF compartment does not seem feasible. In the second part the "Manuilov-system" was modified. An indwelling guiding tube was implanted and fixed with a horseshoe shaped plate to the occipital bone. Puncture can be made on the awake dog without local anaesthetic and produces samples of 1.5 to 2.0 ml CSF for up to 30 days without complications.

Lidaprim, a new bactericidal combination of trimethoprim and sulfametrol, was administered to 20 patients of a paediatric surgical ward over a period of 7 or more days. Analytic determination of plasma and urine concentrations of the chemotherapeutic agent showed homogeneous drug levels at the chosen dosage. No cumulation was observed. Drug tolerance was excellent. Only one patient developed urticaria when the substance was given together with penicillin, but it was not necessary to stop medication in this case.