Penetration of praziquantel into cerebrospinal fluid and cysticerci in human cysticercosis.

Two patients with cysticercosis received praziquantel (PZQ) 75 mg/kg/day orally together with 30 mg prednisone daily for 3 weeks. The first patient presented with grand-mal seizures, a pyramidal tract syndrome and subcutaneous cysticerci, and the other had internal hydrocephalus necessitating drainage. Serial plasma samples were taken after the first dose of PZQ. Lumbar CSF was obtained from the first patient and ventricular CSF from the second. Subcutaneous cysticerci were removed from the first patient. PZQ in the specimens was assayed by GLC. For distribution between plasma and CSF a rate constant of 4.9 h-1 for free PZQ, corresponding to a t1/2 of 8 min or less for the non-protein bound fraction was calculated for Patient 1. In the second patient the distribution was so rapid that the rate constant could not be calculated. The difference in distribution rate might have been due to use of different sampling times or to a time lag in the entry of PZQ between the ventricles and the lumbar sac. The rate constant for distribution of the drug between plasma and parasites was 1.4 h-1, corresponding to a t1/2 of 30 min or less. Thus PZQ penetrates rapidly into the CSF. It enters the parasite more slowly, although still more rapidly than the plasma half-life of PZQ (1-1 1/2 h).

Praziquantel in the cerebrospinal fluid in neurocysticercosis.

In 10 patients with neurocysticercosis (NC), an assessment was made of the praziquantel (PZQ) concentration in the cerebrospinal fluid (CSF), in non-deproteinized serum and in protein-free serum: before administration of the drug and the 1st., 7th. and 21st. days of oral administration (50mg/kg/day during 21 days). Samples of CSF and blood were collected three hours after the last administration of the daily total dosage, on the 1st. and 21st. days; and from 2 to 6 hours after drug administration on the 7th. day. The total daily dosage was distributed into three equal parts of 1/3 each, with a 4 hours' interval between intakes, except in the last 5 cases, who on the 21st. day only were given the total daily dosage on a single administration. Results have shown dispersion in serum concentrations, which are similar to those seen in normal subjects as recorded in literature. There is a correlation between PZQ levels in the CSF and in the serum, the latter being very close to those found in protein-free serum fraction. The statistical treatment of results allowed the following considerations: PZQ concentrations in the CSF and in the protein free serum are in balance from the pharmacodynamic standpoint on the first day; this balance is maintained up to the 21st. day although at different levels from those seen on the 7th. day; on the 21st. day PZQ contents in CSF goes back to its similar values as recorded on the 1st. day, and this suggests that the participation of drug interaction factors has been reduced to non-significant levels. However, several factors can influence PZQ concentration in CSF, as absorption rate, liver first-pass effect and blood-brain barrier changes, and individual dose should be established for each patient based on drug concentration monitoring in the serum and/or in the CSF.

Treatment with praziquantel in a patient with schistosomiasis and chronic renal failure.

The pharmacokinetics of praziquantel in a uraemic patient, infected with Schistosoma haematobium, undergoing haemodialysis, was studied by repeated analyses of serum, urine and dialysis fluid. The results indicate the possibility of treating advanced cases of infection with S. haematobium with the normally recommended doses.

[A comparison of two preoperative medications: responses in sedative, psychic and somatic effects (author's transl)]. / Vergleich zweier Prämedikationsmethoden: Psychische, sedative und somatische Reaktionen.

The influence of two different premedication methods on the psychic reaction of the patient and their somatic-vegetative effect was tested in a controlled double-blind study. 96 patients between the ages of 20 and 40 took part in the study and were divided into two groups. Group 1 (n = 47) received meperidine (Alodan) and promethazine (Phenergan). Group 2 (n = 49) were given thalamonal. All patients underwent a personality test (Cattell 16 PF) a day prior to scheduled surgery. After administration of the respective pre-anaesthetic drugs, three different test methods were applied to determine their subjective state. Simultaneously, independent from the patients, their psychic reactions were determined by the anaesthetist. Premedication 2 effected less calm, i.e. decrease of fear, exhaustion and depression, than premedication 1. The somatic-vegetative region exhibited no significant difference except for increased cardiocirculatory symptoms in group 1. Based on the less favourable psychodynamics in patients who received thalamonal, it is not advised as pre-anaesthetic medication.

Clinical pharmacology in normal volunteers of praziquantel, a new drug against schistosomes and cestodes. An example of a complex study covering both tolerance and pharmacokinetics.

The tolerance of Praziquantel (2-cyclohexylcarbonyl-1, 3, 4, 6, 7, 11b-hexahydro-2H-pyrazino-[2, 1-a]isoquinoline-4-one) in oral doses of 1 X 20 mg/kg, 1 X 50 mg/kg, 3 X 10 mg/kg and 3 X 25 mg/kg body weight (tau = 4 h) was tested in a complex study involving 36 healthy volunteers. In addition to the usual assessment of clinical chemistry, haematology, coagulation physiology, urinalysis, clinico-physiological examination including EEG, and medical examination, clinico-psychological parameters were also recorded and special neurological investigations were performed. No clinically relevant changes were found in any of the laboratory parameters, nor in the medical-neurological or clinico-physiological examinations. Based on a few clinico-psychological parameters and subjective comments, the largest daily dose tested (3 X 25 mg/kg = 75 mg/kg) produced a slight, transient disturbance in general well-being, which was barely detectable on objective clinical examination. The pharmacokinetic behaviour was dominated by rapid metabolism and pronounced first-pass metabolism of praziquantel, which greatly limits the value of results obtained by GC analysis of unchanged drug in serum. The peak concentration in serum was reached after 1--2 h, and the elimination half-life for the period 2--8 h was 1--1.5 h.

[Hormone profiles and hormone therapy in early pregnancy (author's transl)]. / Hormonprofil und Hormontherapie in der Frühschwangerschaft.

Hormone profiles in early pregnancy were established in 67 women and correlated to simultaneously performed ultrasonic examinations. Normal values for human chorionic gonadotropin (HCG), human chorionic somatotropin (HCS), oestradiol (E2) and progesterone (P) were established from the data obtained in 30 early pregnancies which culminated in the birth of a living child. Lowered HCG values were found in 17 out of 23 pregnancies which ended in miscarriage. In these cases ultrasonic examination failed to detect any heart action. Lowered HCS values after the 9th week of pregnancy are also certain proof of missed abortion. P and E2 values are shown to be a parameter reflecting activity of the corpus luteum graviditatis. In clomiphene- and gonadotropin-induced pregnancies higher values were found than in pregnancies managed by substitution treatment with twice weekly 10 mg oestradiolvalerianate + 500mg 17alpha-hydroxyprogesteronecapronate. Lowered P and E2 values with HCG values in the normal range indicate imminent insufficiency of the corpus luteum graviditatis. Pros and cons of hormonal therapy in early pregnancy are discussed.

Controlled clinical trial of mepiprazole in irritable bowel syndrome.

The effect of a new tranquillizer, mepiprazole, in the treatment of the irritable bowel syndrome has been studied in a double-blind cross-over trial in 19 patients. After examination to exclude organic disease the patients were followed up over two treatment periods of four weeks each under either placebo or the active principle, each patient being his own control. The results indicated that the drug had a beneficial effect (P < 0.05) provided that it was given for a period of at least three weeks.