roles of cytochrome P450 and P-glycoprotein in the pharmacokinetics of florfenicol in chickens

The effects of three selective oral inhibitors, fluvoxamine [FLU], ketoconazole [KET], and verapamil [VER], on the pharmacokinetics [PK] of florfenicol [FFC] were investigated in chickens. The chickens were administered orally with saline solution [SAL], FLU [60 mg/kg], KET [25 mg/kg], or VER [9 mg/kg] for 7 consecutive days. Florfenicol was given to the chickens at a single dose of 30 mg/kg orally. Blood samples were collected from each chicken at 0 to 12 h post-administration of FFC. The plasma concentration of FFC was analyzed by high-performance liquid chromatography [HPLC]. The AUC of FFC increased and the Cl[s] of FFC decreased with oral co-administration of KET in chickens, and the C[max] of FFC increased with VER. While the AUC, the Cl[s] and the C[max] of FFC were all invariable with FLU. These data suggested that CYP 3A played a key role in the PK of FFC in chickens, however, P-glycoprotein [P-gp] and CYP 1A did not. The results imply that the adverse drug-drug interaction may occur in the use of FFC if the co-administrated drugs are the substrates, inducers or inhibitors of CYP 3A or/and P-gp

Prediction of the aquatic toxicity of phenols to tetrahymena pyriformis from molecular descriptors

The purpose of this work is to develop robust and interpretable quantitative structure "activity relationship [QSAR] odels for assessing the aquatic toxicity of phenols using a combined set of descriptors encompassing the logP and recently developed variables [Monconn-Z variables]. The used dataset consists of 250 chemicals with toxicity data to the ciliate Tetrahymena pyriformis. For each compound, a total of 197 physico-chemical descriptors including logP and Molconn-Z descriptors were calculated. Multiple linear regression [LR] and Partial least squares [PLS] were used to obtain QSARs and the predictive performance of the proposed models were verified using external statistical validations. The results of stepwise-MLR analysis reveal that the AlogP, MlogP and ClogP models were not successful for the prediction of aquatic toxicity for all the compounds. And by using the logP [AlogP and MlogP] with Molconn-Z descriptors, the obtained QSARs were not successful enough until removal of some outliers. Two optimal QSARs were built with R[2] of 0.71 and 0.70 for the training sets and the external validation Q[2] of 0.69 and 0.68 respectively. All these selected descriptors in the best models account for the hydrophobic [AlogP, MlogP] and other electrotopological properties like SHCsatu, Scarboxylicacid, SHBa, gmax and nelem. PLS produces a good model using all the calculated descriptors with R[2] of 0.78 and Q[2] of 0.64, and hydrophobic and electrotopological descriptors show importance for the prediction of phenolic toxicity

Rotavirus surveillance data from Kunming Children's Hospital, 1998 - 2001 / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the epidemiological status on rotavirus diarrhea in Kunming to improve the rotavirus vaccine immunization program.</p><p><b>METHODS</b>A hospital-based sentinel surveillance program for rotavirus was set up among children less than 5 years old with acute diarrhea in Kunming Children's Hospital. Clinical information and fecal specimens were collected and rotavirus were detected by polyacrylamide gel electrophoresis (PAGE) and/or enzyme linked immunosorbent assay (ELISA). Positive specimens were further serotyped or genotyped by ELISA and/or RT-PCR.</p><p><b>RESULTS</b>During the three years of surveillance, 466 specimens were collected. Rotavirus were detected on 246 (52.8%) specimens. 97% of the rotavirus diarrhea cases occurred among children less than 2 years old. There was a peak of admissions for rotavirus diarrhea cases between October and December which accounted for 48% of all the rotavirus hospitalizations each year. Among 204 specimens with G serotyping, the predominant strain was serotype G1 (47.5%) followed by G2 (17.6%), G3 (15.7%), G9 (4.9%) and G4 (1.0%). Mixed infection (2.5%) were rare and 22 specimens (10.8%) remained non-typeable. P genotyping showed P[4], P[8] and P[6] were the most common strains, accounting for 29.3%, 27.6% and 13.8% respectively. P[4]G2 was the most common strain which accounted for 34.1% (14/41) followed by P[8]G1 (29.3%) and P[6]G9 (12.2%). Another 7 uncommon P-G combinations were also identified.</p><p><b>CONCLUSION</b>Rotavirus was the major cause of acute diarrhea in Kunming. An effective rotavirus vaccine for prevention and control of rotavirus diarrhea should be developed.</p>