Pharmacokinetics and safety of fluconazole and micafungin in neonates with systemic candidiasis: a randomized, open-label clinical trial.

AIMS: The pharmacokinetics (PK) of fluconazole and micafungin differ in neonates compared with children and adults. Dosing instructions in product labels appear to be inconsistent with the emerging scientific evidence. Limited information is available on the safety profile of these agents in neonates. Our objective was to study the population PK and safety of both drugs, randomly administered in neonates with suspected or confirmed systemic candidiasis. METHODS: Neonates were randomized 1:1 to fluconazole (loading dose 25 mg kg-1 ; maintenance dose 12 mg kg-1 day-1 or 20 mg kg-1 day-1 , respectively, for infants <30 weeks or ≥30 weeks' corrected gestational age) or micafungin (loading dose 15 mg kg-1 day-1 ; maintenance dose 10 mg kg-1 day-1 ). PK samples were taken on treatment days 1 and 5. Population parameters were determined using NONMEM and Monte Carlo simulations performed to reach predefined targets. Clinical and laboratory data, and adverse events were collected up to 36 weeks' corrected gestational age or hospital discharge. RESULTS: Thirty-six neonates were enrolled. The median (range) gestational age was 28.2 (24.1-40.1) and 26.8 (23.5-40.0) weeks for fluconazole and micafungin, respectively. Based on 163 PK samples, the median population clearance (l h-1 kg-1 ) and volume of distribution (l kg-1 ) for fluconazole were: 0.015 [95% confidence interval (CI) 0.008, 0.039] and 0.913, and for micafungin were: 0.020 (95% CI 0.010, 0.023) and 0.354 (95% CI 0.225, 0.482), respectively. The loading dose was well tolerated. No adverse events associated with micafungin or fluconazole were reported. CONCLUSION: Based on Monte Carlo simulations, a loading dose for fluconazole and dosing higher than recommended for both drugs are required to increase the area under the plasma drug concentration-time curve target attainment rate in neonates.

[Transrectal prostatosonography. Follow-up in prostate cancer therapy]. / Transrektale Prostatasonographie. Verlaufskontrollen während der Prostatakarzinomtherapie.

Thirty-five cases of prostate carcinoma were followed after orchiectomy and during drug therapy using both ultrasound and digital palpation to measure the prostate. Following orchiectomy and drug therapy the prostate shrunk an average of one third within six months independent of the grading and staging of the carcinoma. The biggest shrinkage was observed in the first two months after therapy. There was agreement between transrectal ultrasonography (TPS) and digital palpation in judging the prostate capsule in two thirds of the cases. Ultrasonographically, a downstaging of the capsule in twenty per cent and an upstaging in fourteen per cent of the cases was found. Three quarters of the G II prostate carcinomas improved ultrasonographically in structure and capsule in the twelve month period of observation while two thirds of the G III prostate carcinomas did not improve. According to our results the routine use of TPS seems not to be indicated when only gross measurement is desired. However TPS is an objective and reliable method für testing the effects of medication on prostate carcinomas.

[Sonography of the efferent urinary tract. Suprapubic and intravesical methods]. / Sonographie der ableitenden Harnwege. Suprapubische und intravesikale Methode.

The ability of sonographic methods to demonstrate the urinary passages and their abnormalities were studied systematically. The ureters can only be demonstrated if they are dilated. Sonography of the bladder can be used as a screening method for tumours, diverticula and stones. Intravesical sonography is useful for staging of bladder tumours. The value of these methods is discussed.

[Transrectal prostate sonography in early cancer recognition]. / Die transrektale Prostatasonographie in der Krebsfrüherkennung.

Within a mass screening program 1016 patients were investigated by transrectal ultrasound. There is generally good correlation of palpation and ultrasound diagnostic. However, prostate carcinoma was less frequently suspected by ultrasound, 2 prostate carcinomas and 1 bladder carcinoma were detected, one prostate carcinoma was missed. The value of the method is discussed.

[The image of prostatic adenoma and cancer in transrectal sonography]. / Das Bild des Prostataadenoms und -karzinoms bei der transrektalen Sonographie.

The transrectal ultrasonography of the prostate is introduced. The sonographic appearance of the adenoma and carcinoma in 357 histologically proven cases is evaluated. Shape, symmetry and definition of the capsule are more reliable differential criteria than the internal echogenicity. The sensitivity is 96.6% for adenoma and 84.2% for carcinoma, whereas the sensitivity of palpation is 91.7% and 77.5% respectively. 6 early cancers are detected. Since infiltration of the capsule and the seminal vesicles can be seen, staging of carcinoma is considerably improved. Accurate measurement of the prostatic size helps in operative planning. Indication and diagnostic value of the method are discussed.

[Transrectal prostatic sonography (TPS)]. / Die transrektale Prostatasonographie (TPS).

A new imaging method of the prostate is described. After the introduction of a sonographic transducer into the rectum, the prostate, the urinary bladder and the seminal vesicles are scanned. Typical transverse sonograms of benign hypertrophy, abscess, calculous disease and carcinomas are presented. The value of this method and its indications are discussed.