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The objective of the present study was to evaluate the pharmacokinetic parameters for both S- and R-ibuprofen enantiomers in very premature neonates (gestational age strictly inferior to 28 weeks) and possible relationships between the pharmacokinetic parameters and various covariates. Newborns were randomized to receive ibuprofen or placebo for the prophylactic treatment of patent ductus arteriosus (PDA) at an initial dose of 10 mg/kg ibuprofen within 6 hours after birth, followed by two 5-mg/kg doses at 24-hour intervals (n = 52). If a PDA was still present afterwards, a curative course of ibuprofen using the same dosage regimen was administered (n = 10). A sparse sampling strategy was used because only 2 samples were collected after the third prophylactic injection and 1 after the third curative injection. A model including the chiral transformation of R- to S-ibuprofen was fitted to the concentration-time data using a population approach (NONMEM). R- and S-ibuprofen t(1/2) were about 10 hours and 25.5 hours, respectively. After prophylactic treatment, the mean clearance of R-ibuprofen (CLR = 12.7 mL/h) was about 2.5-fold higher than for S-ibuprofen (CLS = 5.0 mL/h). In addition, clearance of R- and S-ibuprofen increased significantly with gestational age. The mean estimation of R-ibuprofen clearance was found to be higher than for S-ibuprofen, and the clearance of both enantiomers increased with gestational age. This should be considered to assess pharmacokinetic-pharmacodynamic relationships of ibuprofen in premature neonates and subsequently to understand and refine the use of ibuprofen in managing PDA either as a prophylactic or curative treatment. [ABSTRACT FROM AUTHOR]

A spleen-derived immunosuppressive peptide (SDIP) has been purified to homogeneity. Its physicochemical properties (electrophoretic mobility, u.v. spectra, absence of dansyl derivative) and its enzymatic susceptibilities (proteolytic enzymes, RNase, and DNase) were similar to those of the thymic hormone 'FTS'. SDIP and FTS were eluted with identical retention times in high performance liquid chromatography analysis in three different systems. When tested in sheep cell rosettes, and in the FTS radioimmunoassay in J.F. Bach's laboratory, SDIP presented an activity similar to FTS. In order to compare the thymic hormone to SDIP the biological activity of FTS was determined in in vivo and in in vitro humoral immunity reactions to a T- dependent antigen. As SDIP, FTS inhibited in vivo and in vitro the 19S-bearing cell formation during the last step of the differentiation of the lymphocytes, in the same range of concentration. The two factors appeared to stimulate the incorporation of [³H]-thymidine into the DNA of short-term cultures of thymocytes. The similarity of biological properties of SDIP and FTS together with the similarity observed in the physico-chemical and biochemical properties led to the conclusion that bovine spleen contains a factor similar to FTS. [ABSTRACT FROM AUTHOR]

Some biological properties of a highly-purified non-cytotoxic spleen-derived immunosuppressive peptide (SDIP) have been investigated. SDIP was shown to inhibit the primary anti-sheep red blood cell (SRBC) response at the last step of differentiation of the lymphocyte. In the present study we demonstrated that this response seemed to be T- and adherent spleen-cell dependent as no inhibition was noticed either in the response to TNP-LPS, a T-independent antigen, or in the response to SRBC in adherent spleen cell-depleted cultures. SDIP activity did not occur through an inhibition of sptenocytes DNA synthesis since [3H]-thymidine ([3H]-TdR) incorporation was not modified in mitogen or allogenic stimulated cultures. Conversely, SDIP could act through a stimulation of a T-cell subset as a low specific increase of [3H]-TdR was noticed in cultured thymocytes. [ABSTRACT FROM AUTHOR]

In earlier skin pharmacokinetic studies we have shown that terbinafine is rapidly delivered to the stratum corneum, nails and hair both through sebum and by direct diffusion through dermis-epidermis. In the present study the skin pharmacokinetic profile of terbinafine was studied in two groups of eight human male volunteers during and after 250 mg orally once daily for 7 and 14 days. In the 7-day study high terbinafine levels were found in sebum (19.0 μg/g) and stratum corneum (2.5 μg/g), and a concentration in stratum corneum above the minimal inhibitory concentration for most dermatophytes was still found 48 days after the last day of medication. Terbinafine was found in peripheral nail clippings after 7 days of medication and the concentration was, in the 7-day study, 0.5 μg/g 1 day after stopping medication; it was still 0-2 μg/g 90 days after stopping treatment. The results in the 14-day study were in parallel with, but higher than, in the 7-day study. The elimination of terbinafine from several compartments is biphasic, with a faster initial elimination followed by a slower secondary elimination. For nails, the elimination is slower compared with the other compartments. The results indicate that terbinafine may be effective in shortterm treatment of several dermatophytoses. The concentration of 0.2 μg/g of terbinafine found in nails 90 days after stopping medication, following 7 days of treatment, indicates that the duration of therapy, even in tinea ungium, may be shorter than is currently the case. [ABSTRACT FROM AUTHOR]

The distribution of terbinafine in stratum corneum dermis-epidermis (without stratum corneum), sebum, hair, nails and plasma was studied in human male volunteers during and after 250 mg orally once daily for 28 days. The highest concentration was seen in sebum, 56.07 micrograms/g, after 14 days of therapy. The concentration was still 1.0 microgram/g 44 days after stop of medication. In stratum corneum the highest concentration, 14.4 micrograms/g, was seen 1 day after the last day of therapy, and it was 2.1 micrograms/g 44 days after stop of medication. The concentrations in hair and nails were lower with a maximum of 2.36 and 0.39 micrograms/g respectively, 1 day after stop of therapy, and still 0.21 microgram/g in hair and 0.09 microgram/g in nails 55 days after the last day of medication. With the exception of nails, all other tissue levels were at all times above the plasma concentrations. For nails, tissue levels exceeded that of plasma as early as 1 day after stop of medication, and this difference continued to increase until the last day of tissue sampling, 55 days after the last tablet. These results indicate that terbinafine is delivered to the stratum corneum through sebum and to a minor extent by direct diffusion through dermis-epidermis. Probably short-term therapy with terbinafine may be effective in the treatment of several dermatomycoses, due to the strong binding of terbinafine to stratum corneum for a long time after stop of medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Looking for a "lymphocytic chalone" in Bovine spleen extracts, we isolated an immunosuppressive peptide, whose biochemical and biological properties are identical to those of the serum thymic factor FTS. This factor appeared to be a regulator of the humoral immune response.