Clonidine pharmacokinetics in pregnancy.

The objective of this study was to determine the pharmacokinetic parameters of clonidine during pregnancy compared with previously published data in nonpregnant subjects. Serial blood and urine samples were collected in 17 women during mid to late pregnancy over one steady-state dosing interval to determine clonidine noncompartmental pharmacokinetic parameters (n = 17) and creatinine clearance. In six of these pregnant subjects, maternal and umbilical cord (venous and arterial) plasma samples were collected at the time of delivery for measurement of clonidine concentrations. Clonidine apparent oral clearance was found to be 440 +/- 168 ml/min during pregnancy compared with 245 +/- 72 ml/min as previously reported in nonpregnant subjects (p < 0.0001) (Cunningham et al., 1994). There was a strong correlation (r = 0.82, p < 0.001) between clonidine renal clearance, adjusted for variation in glomerular filtration rate, and urine pH. Umbilical cord to maternal plasma clonidine concentration ratios were 1.0 +/- 0.1 (arterial) and 1.0 +/- 0.1 (venous). In conclusion, clonidine is cleared more rapidly in pregnant women than in nonpregnant subjects. At the time of delivery, the fetus is exposed to similar plasma clonidine concentrations as the mother.

Effects of pregnancy on CYP3A and P-glycoprotein activities as measured by disposition of midazolam and digoxin: a University of Washington specialized center of research study.

The objectives of the study were to evaluate the effects of pregnancy on CYP3A and P-glycoprotein (P-gp) activities, as measured by disposition of midazolam and digoxin, respectively. Thirteen women received digoxin (0.25 mg p.o.) and midazolam (2 mg p.o.) in random order, separated by 1-2 weeks at 28-32 weeks gestation, and the same order was repeated at 6-10 weeks postpartum. Plasma and urine concentrations were determined by liquid chromatography-mass spectrometry and analyzed by noncompartmental methods. Midazolam CL/F(unbound) (593 +/- 237 l/min vs. 345 +/- 103 l/min; P = 0.007), digoxin CL(Renal, unbound) (272 +/- 45 ml/min vs. 183 +/- 37 ml/min; P < 0.002) and digoxin CL(secretion,) (unbound) (109 +/- 34 ml/min vs. 58 +/- 22 ml/min; P < 0.002) were higher during pregnancy than postpartum. These data are consistent with increased hepatic and/or intestinal CYP3A and renal P-gp activities during pregnancy.

Amoxicillin pharmacokinetics in pregnant women: modeling and simulations of dosage strategies.

Amoxicillin is recommended for anthrax prevention in pregnancy. The objective of this study was to evaluate the pharmacokinetics of amoxicillin during pregnancy and postpartum (PP). Sixteen women received amoxicillin during gestation (18-22 weeks (T2) and 30-34 weeks (T3)) as well as 3 months postpartum (PP) to evaluate single-dose pharmacokinetics. Amoxicillin compartmental pharmacokinetic parameters were used to simulate amoxicillin concentration-time profiles following different dosage strategies. Amoxicillin CL(renal) (T2: 24.8+/-6.7 l/h, P<0.001; T3: 24.0+/-3.9 l/h, P<0.001; and PP: 15.3+/-2.6 l/h) and renal CL(secretion) (T2: 280+/-105 ml/min, P<0.002; T3: 259+/-54 ml/min, P<0.001; and PP: 167+/-47 ml/min) were higher during pregnancy than postpartum. Simulations suggest that amoxicillin concentrations adequate to prevent anthrax may be difficult to achieve during pregnancy and postpartum. Increases in amoxicillin CL(renal) and renal CL(secretion) reflect increases in filtration and secretory transport or diminished reabsorption in the kidneys. Amoxicillin may not be an appropriate antibiotic for post-anthrax exposure prophylaxis.

Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of human parotid salivary proteins.

The proteins in human parotid saliva have been separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis into 20 or more well resolved species. The Coomassie Brilliant Blue (CBB) R-250 and silver staining procedures have been modified to overcome the problems encountered with staining of proline-rich proteins. By means of the CBB R-250 procedure which stains proline-rich proteins pink-violet, immunoblotting, concanavalin A binding, periodate-Schiff staining and zinc binding, all of the major proteins have been characterised. Substantial individual-to-individual differences were observed in the protein patterns formed. Comparison of parotid, submandibular, and whole saliva from a single individual indicated that fewer proline-rich proteins are expressed in submandibular saliva than in parotid, but whole saliva contains much lower levels than either duct secretion. The results will form a useful base for future research into the functions of salivary proteins.

Laboratory microcomputer system for the development of microcomputer-controlled analytical instrumentation.

Researchers in analytical procedures can acquire greater control over their experimental parameters, procedures and the mathematical operations used to manipulate and evaluate their data, by incorporating microcomputer technology into their laboratory instrumentation. A hybrid microcomputer system has been assembled to aid in the development of microcomputer-controlled analytical instrumentation and to enhance performance of microcomputer-controlled instrumentation through improved logic sequencing. Fundamental hardware modules, including the central processing, memory and input/output are specified. These modules are described in terms of the hardware system features necessary for effective programming capabilities. Included are those dealing with burning of programs on erasable programmable read only memory and with the types and sizes of memories required. Software elements are described in terms of system programming features required for creating and incorporating the desired logic sequencing into analytical instrumentation. Although language selection and installation are not examined in complete detail, some problems encountered in this area are discussed.

Concentration of mercury in animal products and soils of North Dakota.

Total mercury (Hg) was determined in milk, eggs, beef, pork, human head hair, soil and water obtained from four geographical areas of North Dakota. The sampling areas were selected on the basis of differences in prevalent agricultural practices, climate and topography. Statewide average Hg concentrations in ppb were milk, 0.8; eggs, 12; beef muscle, 5; beef liver, 10; pork muscle, 11; pork liver, 15; head hair, 1708; soil, 30; rainwater and well water, less than one. There were no significant differences observed among areas in Hg content of any substance sampled except beef muscle. Beef muscle obtained from areas 2 and 4 contained significantly (P less than or equal to 0.05) higher levels of Hg than beef muscle from the other two areas. However, the magnitudes of differences were small (4 to 6 ppb). Considerable variation among individual beef and swine were noted but only six beef of 453 sampled and three swine of 156 sampled had tissue Hg exceeding 50 ppb. Appreciable variation was observed in Hg in eggs with respect to farms within an area, eggs from the same farm, and sampling times within a year. Few eggs sampled contained more than 50 ppb. Significantly (P less than or equal to 0.01) higher levels of Hg were found in head hair of women as compared with men and relatively large differences among individuals were observed. Average Hg in hair was generally low irrespective of sex of donor or area of the state as compared with data given in the literature. Soil Hg levels were consistently low in all areas of the state, and no relationship between cropping practices and soil Hg was detected.