Parathyroid hormone-related protein in the colostrum of paretic post parturient dairy cows.
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Animals↗
Biomedical subjects
J L Riond
Publications and source records attributed to J L Riond.
Sprayed medicated feed with sulfadimidine for piglets.
The bioavailability of two different forms of medicated feed containing 2000 mg sulfadimidine (SDM) per kg was determined in three groups of eight piglets. In the first group, pharmacokinetic parameters of SDM were determined after a single intravenous dose of 10 mg/kg body weight and after single oral doses of 45 mg/kg body weight ingested either as an oleus solution sprayed directly onto the feed pellets ready for use (SPR) or as a commercially available premix incorporated into the feed before pelletising (PMX). After the single intravenous administration, the mean +/- SD of the volume of distribution was 0.34 +/- 0.05 l/kg, the total body clearance 0.37 +/- 0.07 ml/min.kg, the mean residence time 15.5 +/- 2.5 h, and the elimination half-life 11.1 +/- 2.0 h. Although no statistical significance existed, a single meal with PMX was associated with slightly higher mean values for the maximum serum concentration (Cmax), the time to reach Cmax, and the bioavailability (52.98 +/- 6.60 micrograms/ml, 6.8 +/- 1.1 h, 59.7 +/- 12.1%, respectively, vs. 40.04 +/- 13.19 micrograms/ml, 6.0 +/- 1.4 h, 49.0 +/- 18.6 for SPR). The remaining two groups of piglets received medicated feed with either SPR or PMX during a 3-day period both with restrictive (twice-daily) or ad libitum feeding according to a cross-over design. In all four cases, potentially efficacious plasma SDM concentrations between 50 and 150 micrograms/ml were obtained within 24 h after initiation of the treatment. With PMX, plasma concentrations tended to be higher than with SPR with both feeding regimens. Ad libitum feeding was associated with a significantly higher food intake and hence a higher SDM intake resulting in higher plasma concentrations. Additionally, plasma concentrations were more constant over time with ad libitum feeding whereas they declined considerably between meals in restrictively fed animals. In vitro dissolution tests of the two types of medicated feed revealed that SDM was rapidly released from SPR (58% within 15 min) and that SDM release from PMX was markedly slower (3% within 15 min). Despite the relatively slow rate of in vitro dissolution, in vivo absorption of SDM was satisfactory. It is concluded that both forms of SDM medicated feed may be considered bioequivalent and potentially efficacious in piglets.
Administration, Oral↗
Clarithromycin pharmacokinetics after oral administration with or without fasting in crossbred beagles.
Clarithromycin was administered to eight dogs intravenously and orally. A suspension or a tablet was given to animals both immediately after feeding and on an empty stomach. Neither the formulation nor the time of administration in relation to feeding significantly influenced the pharmacokinetic parameters. The lowest mean (+/-SD) maximum plasma concentration (Cmax) of 3.0 +/- 0.6 micrograms/ml, the lowest bioavailability (F) of approximately 69 per cent and the shortest time above the proposed breakpoint of susceptibility (L) of 2.9 +/- 1.3 hours were observed with the suspension after feeding. The highest Cmax of 3.6 +/- 0.8 micrograms/ml, the highest F of 83 per cent and the longest L of 4.5 +/- 2.0 hours were observed with the suspension in the fasted group. The mean time at which Cmax occurred (tmax) was between one and two hours after administration. In conclusion, clarithromycin is potentially suitable for therapeutic use in dogs, pending species-specific studies of safety and therapeutic efficacy.
Administration, Oral↗
The concentration of ionized magnesium in serum during the periparturient period of non-paretic dairy cows.
Ion-selective electrodes have recently been designed for determining the ionized concentration of magnesium (Mg2+) in serum. This development may allow new insights into some metabolic diseases of cattle. For this report, the concentrations of Mg2+, total magnesium (Mgtot), ionized calcium (Ca2+), total calcium (Catot), and inorganic phosphate (P(i)) were determined in sera from seventeen 3- to 16-year-old Brown Swiss and crossed Simmental/Red Holstein cows during the periparturient period. In each animal, a transient increase of Mg2+ and Mgtot serum concentrations was observed in association with the transient decrease in serum concentrations of Ca2+, Catot and P(i) after parturition. On average, throughout the study, the serum Mg2+ concentrations were 68.5% of those of Mgtot, whereas the serum Ca2+ concentrations were 52% of those of Catot. The possible mechanisms involved in the transient increase of Mg2+ and Mgtot serum concentrations are discussed.
Animals↗
Parathyroid hormone-related protein and calcium concentrations in milk and blood of ewes.
Parathyroid hormone-related protein (PTHrP) and calcium (Ca) concentrations were measured 2 to 3 months postpartum in milk and plasma or serum of 22 ewes by the use of commercial radioimmunoassay kits for PTHrP concentration, colorimetry for serum total Ca concentration (Catot), and atomic absorption spectrophotometry for milk total Ca concentration. Scatter plots did not reveal dependency between milk Ca and Catot, Catot and plasma PTHrP, milk Ca and milk PTHrP, and milk PTHrP and plasma PTHrP. Thus, the systemic and mammary effects of PTHrP are not major determinants of the endocrine, paracrine, and autocrine regulation of Ca homeostasis during lactation in ewes.
Animals↗
Postparturient hypocalcemia of dairy cows: a model for the study of the interdependence of Ca, Pi, and Mg homeostasis.
Disorders of calcium, phosphorus and magnesium homeostasis in ruminants provide natural models for the study of the physiology and pathophysiology of these minerals. The knowledge that can be acquired with a better understanding of the pathogenesis of these diseases could give useful clues in the puzzle of human osteoporosis. In the present study, the case of parturient paresis of dairy cows is reexamined with a newly developed technique for the measurements of serum ionized magnesium concentrations (Mg2+). The concentrations of total magnesium (Mgtot), ionized calcium (Ca2+), total calcium (Catot), and inorganic phosphate (Pi) were also determined in the sera of seventeen 3- to 16-year-old Brown Swiss and crossed Simmental/Red Holstein cows during the periparturient period. In each animal, a transient increase of Mg2+ and Mgtot serum concentrations was observed in association with the transient decrease after parturition of Ca2+, Catot and Pi serum concentrations. On average, throughout the study, serum Mg2+ concentrations were 68.5% of those of Mgtot whereas serum Ca2+ concentrations were 52% of those of Catot. The possible mechanisms involved in the transient increase of Mg2+ and Mgtot serum concentrations are discussed and the relevance of this data for osteoporosis is outlined.
Analysis of Variance↗
[Parathyroid hormone related-protein and calcium homeostasis].
Recently, parathyroid hormone-related protein (PTHrP) was identified as one of the major causes of humoral hypercalcemia of malignancy in several species. The hormone probably has an important role in the physiology and pathophysiology of mammals and birds. Many endocrine, paracrine and autocrine functions are attributed to PTHrP. Parathormone shares the same receptor with PTHrP. This receptor was isolated in many tissues. PTHrP could be an important fetal growth factor. The influence of PTHrP on calcium homeostasis is presently the object of active research. PTHrP stimulates calcium transfer through the placenta and maintains a concentration gradient between the dam's blood and the fetus. The hormone is produced in large quantities in milk. However, its exact and principal function in lactation has not yet been determined. Among other effects, PTHrP might stimulate the secretion of calcium, phosphate and magnesium in milk and might foster the development of the mammary gland. A role of PTHrP in the pathogenesis of postparturient paresis in dairy cows has been hypothesized. Results of recent trials demonstrate that despite an important role in calcium homeostasis, PTHrP is not pivotal in the development of milk fever.
Amino Acid Sequence↗
Parathyroid hormone-related protein and calcium homeostasis during the periparturient period of dairy cows.
Plasma and milk concentrations of parathyroid hormone-related protein (PTHrP) at various stages of pregnancy and lactation were determined in thirty-nine 3- to 16-year-old Brown Swiss and Red Holstein x Simmental dairy cows originating from 4 herds. Eighteen of the cows were separated into 2 groups: low-parity (LP, n = 8) cows if they were in their first or second pregnancy and high-parity (HP, n = 10) cows if they were in their third or greater pregnancy. Blood samples were collected from each cow on 1 occasion, 15 to 5 days before calving, and blood and milk samples were collected daily during 6 days after calving. Serum total and ionized calcium (Ca(tot) and Ca2+, respectively) and milk Ca(tot) concentrations were also quantified. A transient postpartum decrease of serum Ca(tot) and Ca2+ concentrations was observed, whereas milk Ca(tot) concentration was constant. Plasma concentration of PTHrP was detected in 11 of 21 cows by use of an immunoradiometric assay (range, 0.45 to 1.82 pmol/L). Daily mean (+/- SD) colostrum and milk PTHrP concentrations ranged from 3.25 (+/- 3.23) to 4.69 (+/- 1.36) nmol/L in LP cows and 2.74 (+/- 0.5) to 5.95 (+/- 0.33) nmol/L in HP cows. In all cows of the HP group and most cows of the LP group, milk PTHrP concentration was highest in the day-1 sample. Milk PTHrP concentration correlated positively with milk Ca(tot) concentration in HP cows (r = 0.5959, P < 0.0001). In contrast, there was a negative relation between milk PTHrP and milk Ca(tot) concentrations in LP cows (r = -0.3285, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Variance↗
Comparative pharmacokinetics of aditoprim in milk-fed and conventionally fed calves of different ages.
Aditoprim body disposition was described after intravenous and oral administration of 5 or 10 mg kg-1 bodyweight to milk-fed and conventionally fed calves with bodyweights of 80 kg, 160 kg and 210 kg. After intravenous administration to conventionally fed calves, aditoprim total body clearance increased and elimination half-life decreased with age. Oral administration of aditoprim with feed was associated with a longer absorption half-life and consequently longer elimination half-life in the older calves, because the drug was deposited in a functionally mature rumen. The weak base aditoprim is slowly absorbed from the rumen according to the pH partition hypothesis and probable binding to dietary fibres and other macromolecules. The favourable pharmacokinetics of aditoprim indicate a potential use for this antimicrobial in bovine practice, pending further studies on residue depletion profile, safety and therapeutic efficacy.
Administration, Oral↗
Comparison of an HPLC and bioassay method to determine antimicrobial concentrations after intravenous and oral administration of enrofloxacin in four dogs.
Plasma samples of dogs given 5 mg kg-1 bodyweight of a broad spectrum antimicrobial with the active ingredient enrofloxacin were assayed by two different methods (bioassay: Escherichia coli 14 ICB 4004 on ISO sensitest agar; high performance liquid chromatography with a RP C18 column). At concentrations up to 1000 ng ml-1 a linear correlation between values obtained by the two assay methods was found. At concentrations above 1000 ng ml-1 no correlation could be determined. The main metabolite of enrofloxacin, ciprofloxacin, is an important determinant of overall antimicrobial activity and hence influences bioassay results.
Administration, Oral↗
Modulation of the anabolic effect of synthetic human parathyroid hormone fragment-(I-34) in the bone of growing rats by variations in the dosage regimen.
1. The influence of the time of the day of the administration of synthetic human parathyroid hormone fragment-(1-34) [hPTH-(1-34)] on its anabolic effect in bone was investigated in 23 60-day-old female Wistar rats. Rats were randomly assigned to the groups vehicle control morning, hPTH-(1-34)-treated morning, vehicle control afternoon and hPTH-(1-34)-treated afternoon, and once daily received a subcutaneous injection of 8 micrograms of hPTH-(1-34)/100 g body weight for 11 days. The increase in net intestinal calcium absorption and the increase in calcium balance were not influenced by the time of day of hPTH-(1-34) treatment. Four days after cessation of treatment, the net intestinal calcium absorption and calcium balance in hPTH-(1-34)-treated rats were not different from those of the control rats. 2. Modulation of the anabolic effect by variation of the hPTH-(1-34) dosage regimen was investigated in 43 60-day-old female Wistar rats. Rats were randomly assigned to the groups vehicle control, environmental control, 8 micrograms of hPTH-(1-34)/100 g body weight every 3 days for 24 days, 8 micrograms of hPTH-(1-34)/100 g body weight every 2 days for 16 days, 8 micrograms of hPTH-(1-34)/100 g body weight every day for 8 days, 4 micrograms of hPTH-(1-34)/100 g body weight twice a day for 8 days and 2.7 micrograms of hPTH-(1-34)/100 g body weight three times a day for 8 days. In all cases, the total dose of hPTH-(1-34) received was 64 micrograms/100 g body weight.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intravenous and oral administration of enrofloxacin in dogs.
Four dogs were given 5 mg/kg body weight enrofloxacin intravenously (i.v.) and orally (p.o.) in a cross-over study. Plasma concentrations of the active ingredient enrofloxacin and its main metabolite ciprofloxacin were determined by a reversed phase liquid chromatographic method. Pharmacokinetic parameters of both substances were calculated by use of statistical moments and were compared to those of enrofloxacin described in the veterinary literature. Mean enrofloxacin t1/2 lambda z was 2.4 h, mean Cls was 27.1 ml/min.kg, and mean Vss was 7.0 l/kg. After i.v. and p.o. administration, concentrations of ciprofloxacin exceeding minimal inhibitory concentrations of several microorganisms were reached (Cmax = 0.2 microgram/ml, tmax = 2.2 h after intravenous administration; Cmax = 0.2 microgram/ml, tmax = 3.6 h after oral administration). A considerable part of the antimicrobial activity is due to ciprofloxacin, the main metabolite of enrofloxacin.
Administration, Oral↗
Pharmacokinetics of the gyrase inhibitor marbofloxacin: influence of pregnancy and lactation in sows.
Six pregnant sows were treated in early pregnancy, late pregnancy and during lactation. Marbofloxacin was administered (2 mg/kg body weight) intravenously and orally. The active drug concentration in the plasma was quantitated by use of high performance liquid chromatography (HPLC). Pharmacokinetic parameters were calculated by use of statistical moments. In lactating animals, the concentrations in milk were also determined by HPLC. Mean elimination half-life of the drug after oral administration was significantly shorter in lactating sows (5.74h) than that of the early pregnancy group (10.09h). Total body clearance was highest in the lactating sows (3.27 ml/minute.kg body weight). The volume of distribution was large in all physiological states studied indicating good tissue penetration. Bioavailability was about 80% in pregnant and lactating sows. Antimicrobial secretion in milk contributed greatly to marbofloxacin elimination. These results indicate an important influence of lactation on marbofloxacin pharmacokinetics in sows. Therefore, in such cases, marbofloxacin dose should be increased during lactation.
Administration, Oral↗
Research note: pharmacokinetics of aditoprim in turkeys after intravenous and oral administration.
The pharmacokinetics of aditoprim, a not yet commercialized selective reversible inhibitor of dihydrofolate reductase, were determined in turkeys after intravenous (5 mg/kg BW) and oral (5.46 +/- .44 mg/kg BW) administration. The mean (+/- SD) total body clearance of 26.9 +/- 2.3 mL/min per kg BW was high when compared with that determined for other species, presumably a consequence of the higher metabolic rate of birds. Consequently, mean aditoprim elimination half-life was relatively short (3.3 +/- .2 h). As determined in mammalian species, the apparent volume of distribution at steady state was large. Aditoprim in drinking water (100 and 300 mg/L water) provided plasma concentrations between .08 and .19 micrograms/mL. Circadian rhythms with highest concentrations in the late afternoon and lowest concentrations in the morning were observed. Despite its short elimination half-life, aditoprim may still be a valuable antimicrobial for use in avian medicine pending safety, efficacy, and residue depletion studies.
Administration, Oral↗
Influence of tiamulin concentration in feed on its bioavailability in piglets.
Tiamulin pharmacokinetic parameters were determined in 8 2-month-old male improved Swiss Landrace piglets after intake of 2,000 mg/kg feed, 500 mg/kg feed, 12.5 mg/ml aqueous solution administered via a stomach tube and 180 mg/kg feed offered ad libitum. In all cases, the total tiamulin dose received was 10 mg/kg body weight (bw) per day. For the 2,000 mg/kg and 500 mg/kg treatments, animals were restrictively fed a commercial mix in amounts corresponding to 3-fold their maintenance requirement of digestible energy. The piglets first individually received the amount of medicated feed and immediately thereafter the rest of the daily ration. The highest tiamulin serum concentrations (Cmax), the largest area under the curve (AUC0-->infinity), the largest absorption rate constant (Ka), and the shortest time at which the maximum serum concentration occurred (tmax) were obtained after administration via stomach tube followed in the respective order by the 2,000 mg/kg, 500 mg/kg and 180 mg/kg treatments. Ad libitum feeding of the medicated mix at 180 mg/kg failed to provide tiamulin serum concentration above minimum inhibitory concentrations (MIC) of some representative microorganisms. In conclusion, tiamulin concentration in medicated feed strongly influences its rate and extent of absorption and consequently serum concentrations. Larger tiamulin concentration in feed enhances its bioavailability. The common practice adopted by national regulatory agencies for the registration of a new drug is to conduct pharmacokinetic studies after administration agencies for the registration of a new drug is to conduct pharmacokinetic studies after administration via a stomach tube. This practice should be reevaluated because this mode of administration does not correspond to that in routine use.
Administration, Oral↗
Pharmacokinetics and bioavailability of spiramycin in pigs.
The pharmacokinetics of spiramycin in pigs were investigated after intravenous and oral administration. The potential therapeutically effective blood level was established after a single administration and examined in a subsidiary five day study. The rapid intravenous injection of 25 mg spiramycin/kg bodyweight produced marked salivation in all the test animals. The elimination half-life (2.3 +/- 1.2 hours) was relatively short, in accordance with the total body clearance rate (27.3 +/- 10.1 ml/minute/kg). The high volume of distribution (5.2 +/- 2.2 litres/kg) was due to the accumulation of the drug in the body tissues. The maximum plasma concentration (4.1 +/- 1.7 micrograms/ml) after oral administration of 85 to 100 mg spiramycin/kg bodyweight was reached after 3.7 +/- 0.8 hours and the half-life of the elimination phase was 6.0 +/- 2.4 hours. The oral bioavailability was 45.4 +/- 23.4 per cent. Ad libitum feeding of a diet containing 2550 mg spiramycin/kg produced a steady state concentration of 0.96 +/- 0.27 micrograms/ml. This plasma concentration would provide a potentially therapeutically effective blood concentration against Mycoplasma species, Streptococcus species and Staphylococcus species.
Administration, Oral↗
The influence of age on the pharmacokinetics of aditoprim in pigs after intravenous and oral administration.
Some pharmacokinetic parameters of aditoprim were determined in 3- and 6-month-old pigs. After intravenous administration of 5 mg/kg body weight, the mean total body clearance of the older pigs was smaller than that of the younger pigs. This difference was not reflected in the elimination half-life. After oral administration of 5 mg/kg body weight, the mean absorption rate constant was smaller and the mean absorption half-life was longer in the older pigs. The age-related changes in the pharmacokinetics of aditoprim were not sufficiently pronounced to suggest the necessity of modifying the oral dosage regimen in pigs of this age range. The favourable pharmacokinetics of aditoprim in pigs (large apparent volume of distribution, long elimination half-life and high bioavailability) may permit introduction of this drug into swine practice, after safety and residue depletion studies.
Administration, Oral↗
Cardiovascular effects and fatalities associated with intravenous administration of doxycycline to horses and ponies.
Intravenous use of doxycycline in horses is associated with deleterious side effects on the cardiovascular system which may result in fatalities. At dosages and infusion rates used in these studies, supraventricular tachycardia, systemic arterial hypertension, clinical signs of discomfort, collapse and death were observed. Results of the present study suggest that the intravenous use of doxycycline should be avoided in horses.
Animals↗