Appendix C:  Ampicillin Trihydrate in Cattle updated 12-9-03

 

Ampicillin trihydrate injectable administration

Brown MP, Mayo MB, Gronwall R (1991), Serum and synovial fluid concentrations of ampicillin trihydrate in calves with suppurative arthritis, Cornell Veterinarian 81: 137-143
Ref ID: 306 (mean ± SD timepoint data for serum concentrations after 10 mg/kg ampicillin trihydrate IM.  Also mean ± SD more limited timepoint data for normal and suppurative synovial fluid.  A request was made to the primary author for individual animal data with no response.)

Hjerpe CA (1979), A comparison of serum antibiotic concentrations achieved in calves with intratracheal administration of procaine penicillin G, ampicillin trihydrate, tylosin, oxytetracycline hydrochloride, chloramphenicol, chloramphenicol sodium succinate, dihydrostreptomycin sulfate and neomycin sulfate with those achieved with intravenous, intramuscular and subcutaneous administration, Bovine Practitioner 14: 18-26
Ref ID: 613 (10 mg/lb ampicillin trihydrate mean ± SD serum concentrations after IM (n = 6), SC (n = 6), and intratracheally (n = 3) administration.  Cylinder plate assay)

Hjerpe CA, Routen TA (1976), Practical and theoretical considerations concerning treatment of bacterial pneumonia in feedlot cattle, with special reference to antimicrobic therapy, Proceedings of the 9th Annual Convention of the American Association of Bovine Practitioners 9: 97-140
Ref ID: 231 (same data for 10 mg/lb IM and SC ampicillin trihydrate data as for Hjerpe reference 613, plus 3 mg/lb IM mean ± SD timepoint data for 6 calves.  Cylinder plate assay)

Martinez,MN, W M Pedersoli, W R Ravis, J D Jackson, R Cullison, 2001, Feasibility of interspecies extrapolation in determing the bioequivalence of animal products intended for intramuscular administration: Journal of Veterinary Pharmacology and Therapeutics, v. 24, p. 125-135.
Ref ID: 4201  (Raw data provided by Dr. Martinez)

Nouws JFM, Van Ginneken CAM, Hekman P, Ziv G (1982), Comparative plasma ampicillin levels and bioavailablity of five parenteral ampicillin formulations in ruminant calves, Veterinary Quarterly 4: 62-71
Ref ID: 614 (Complete modeling parameters with variance parameters for Ampicllin Sodium to 6 calves at 15.5 +/- 1.9 mg/kg IV.  Ampicillin trihydrate aqueous timepoint ± SD concentrations after 7.7 mg/kg IM.  Time point data for 6 other non-US Trihydrate formulations  in oily suspensions. )

Supporting articles for injectable administration

Groothuis,D.G., G.Ziv, J.F.M.Nouws, and A.S.J.P.A.M.Van Miert. 1978. "Effects of experimental Escherichia coli endotoxaemia on ampicillin:amoxycillin blood levels after oral and parenteral administration in calves." Journal of Veterinary Pharmacology and Therapeutics. 1:81-84.
Ref ID: 3513  (Ampicillin IM, and Amoxicillin IV and Orally, with and without endotoxin injection.  Serum timepoint data graphical only.)

Nouws JFM, Ziv G (1978), A kinetic study of beta-lactam antibiotic residues in normal dairy cows, Journal of Veterinary Medicine A 25: 312-326
Ref ID: 4443  (Ampicillin trihydrate (12.5 ± 0.94 mg/kg) and Ampicillin sodium (10.12 ± 0.76 mg/kg) IM in dairy cows with reported C₀, b, T_1/2b, K_a, and T_max, and C_max from a one-compartment model)   

Ziv G, Nouws JFM (1979), Serum and milk concentrations of ampicillin and amoxycillin in ruminants, Refuah Veterinarith 36: 104-110
Ref ID: 185  (Ampicillin trihydrate at 12.5 mg/kg IM to cows and  10.0 mg/kg IM to ewes and goats. Serum and mastitic/normal milk data for ampicillin.  However, only graphic presentation.)

See 4980 under oral for supporting IV

Potential articles for joints

See Brown (306) under injectable above

Oral administration

Acred P, Larkin PJ, Mizen L (1966), The distribution of orally administered ampicillin in calves, Veterinary Record 79: 103-104
Ref ID: 5019 (bioassay, 2 calves per timepoint, individual animal timepoint data, gut content, tissue, serum, and urine concentration after 50 mg total dose orally in milk replacer.  Ampicillin form?)

Larkin PJ (1972), The distribution of a 400 mg. dose of ampicillin administered orally to calves, Veterinary Record 90: 476-478
Ref ID: 5011 (Same study design as above, but at 400 mg per calf)

Ziv G, Nouws JF, Groothuis DG, Van Miert AS (1977), Oral absorption and bioavailability of ampicillin derivatives in calves, American Journal of Veterinary Research 38: 1007-1013
Ref ID: 4980 (Ampicillin trihydrate, 1 gram total dose to young calves with and without milk, and also IV.  Time-point concentration data is presented graphically only.  Reported parameters (with variance estimates) for oral administration include F, Lag time, Absorption T1/2, Elimination T1/2, Cmax, Tmax, and AUC.  Reported parameters for IV administration include Elimination T1/2, Vd, and AUC.  Agar plate diffusion assay.)

Supporting articles for oral administration

Palmer GH, Bywater R, Stanton A (1983), Absorption in calves of amoxicillin, ampicillin, and oxytetracycline given in milk replacer, water or an oral rehydration formula, American Journal of Veterinary Research 44: 68-71
Ref ID: 305  (Ampicillin trihydrate, graphical timepoint concentration data only, but has comparative AUC data for administration in "Glucose-Glycine-Electrolyte-Solution" and in milk replacer.)

See reference 3513 under supporting injectable data also.

Milk concentrations after IM injection

Anderson,KL, W A Moats, J E Rushing, D P Wesen, M G Papich, 1996, Ampicillin and amoxicillin residue detection in milk, using microbial receptor assay (Charm II) and liquid chromatography methods, after extra-label administration of the drugs to lactating cows: American Journal of Veterinary Research, v. 57, p. 73-78.
Ref ID: 4743  (Liquid Chromatogrphy and microbial receptor assay methods compared for Ampicillin trihydrate IM 22mg/mg and Amoxicillin trihydrate  IM 22 mg/kg in  Individual milk timepoint data in graphical form. Mean ± SD of milk PK parameters Cmax, Tmax, k C0, t1/2, AUC.  No serum data.)

See reference 185 under supporting injectable data

Intratracheal administration data

See 613 under injectable data.

Intratracheal administration data (supporting)

Long PE, Guarnieri JA, Herbst DV, Teske RH (1983), Disposition of ampicillin administered intravenously and intratracheally to young calves, Journal of Veterinary Pharmacology and Therapeutics 6: 273-279
Ref ID: 176 (Graphical data presentation only of time-point with variance estimate data presented.  Does give comparative bioavailability of intratracheal to IV administration of ampicillin trihydrate.)

Won't use now

Alam,M, A K Sinha, N C Banerjee, 1990, Biokinetic appraisal of ampicillin in cows: Indian Journal of Animal Sciences, v. 60, p. 562-564.
Ref ID: 6169 (Abstract only.)

Black WD (1976), Serum ampicillin levels in the calf:  influence of dosage, route of administration and dosage form, Canadian Journal of Comparative Medicine 40: 341-345
Ref ID: 298 (Data inconsistent with all other references.)

Company Report. Oral absorption of Ampicillin, Amoxicillin and Hetacillin in Calves.  1-5. 2001.
Ref Type: Report
Ref ID: 5770 (Can't locate at this time)

Ehinger AM, Kietzmann M (2000), Tissue distribution of oxacillin and ampicillin in the isolated perfused bovine udder, Journal of Veterinary Medicine A 47: 157-168
Ref ID: 1442 (In-vitro model)

Groothuis DG, Ziv G, Nouws JFM, Van Miert ASJPAM (1978), Effects of experimental Escherichia coli  endotoxaemia on ampicillin:amoxycillin blood levels after oral and parenteral administration in calves, Journal of Veterinary Pharmacology and Therapeutics 1: 81-84
Ref ID: 4382  (Ampicillin trihydrate IM and ampicillin sodium IV at 1 gram standard dose to 40-50 kg calves.  Mean timepoint data does not have variance estimates for the endotoxin + and - groups.)

Groothuis,DG. Pharmacokinetics and the activity of antibacterial agents against Salmonella dublin infection in veal calves.  1983.
Ref Type: Thesis/Dissertation
Ref ID: 3390 (Get if data needed.)

Gustafsson,B, 1980, Disposition of antimicrobial drugs in the female genital system: 9th International Congress on Animal Reproduction and Artificial Insemination, v. 9, p. 485-490.
Ref ID: 4370 (Review article.)

Lashev LD, Pashov DA (1992), Interspecies variations in plasma half-life of ampicillin, amoxycillin, sulphadimidine and sulphacetamide related to variations in body mass, Research in Veterinary Science 53: 160-164
Ref ID: 307  (Summary data from the literature on elimination half-lives only)

Long PE, Guarnieri JA, Herbst DV, Teske RH. Blood and tissue levels of ampicillin in intratracheally and intravenously dosed calves. Journal of Dairy Science 63[suppl 1], 113. 1980.
Ref Type: Abstract
Ref ID: 310 (Very brief abstract with insufficient data, see article 176 under intratracheal data for complete data)

Long,PE, R D Furrow, 1984, Dispersion of fluorescein dye-ampicillin mixture after intratracheal administration in calves: Journal of Veterinary Pharmacology and Therapeutics, v. 7, p. 147-151.
Ref ID: 355 (Not suitable for modeling.)

Montesissa C, Villa R, Sonzogni O, Belloli C, Carli S (1994), Comparative pharmacokinetics of ampicillin-sulbactam combination in calves and sheep, Journal of Veterinary Pharmacology and Therapeutics 17: 359-364
Ref ID: 184 (Graphical presentation of timepoint data only along with compartmental parameter values.  Non-US formulation of ampicillin/sulbactam given IV and IM.)

Palmer GH (1983), The influence of milk replacer, water and an oral fluid replacer on oral absorption of antibiotics in preruminant calves. [Abstract], Veterinary Research Communications 7: 263-264
Ref ID: 4273 (abstract of reference 305)

Roy,DC, M S Bal, 1990, Studies on urinary and biliary clearance of ampicillin in cow calves: Indian Veterinary Journal, v. 67, p. 1021-1025.
Ref ID: 3966 (Abstract only.)

Schifferli,D, J Nicolet, M Wanner, 1981, Therapeutic efficacy of penicillin, ampicillin and spiramycin after parenteral administration to calves: Schweizer Archiv fur Tierheilkunde, v. 123, p. 443-453.
Ref ID: 4328 (In French.  Formulation not in U.S.  Calves given 7 mg/kg of Ampicillin Trihydrate Oily suspension.)

Sepp S. Pharmacokinetics of gentamicin, ampicillin, erythromycin, chlortetracycline and sulfadimethoxine in veal calves after subcutaneous or oral administration. Aus der Medizinischen Tierklinik der Tierarztlichen Fakultat der Universitat Munchen Vorstand . 1986.
Ref Type: Thesis/Dissertation
Ref ID: 4118 (Do not have in file, will require translation)

Stanek VC, Fessl L, Awad-Masalmeh M. Penicillin and ampicillin levels in pathologically changes tissues after intravenous regional antibiosis in cattle extremities. Berliner und Munchener Tierarztliche Wochenschrift 97[5], 162-166. 1984.
Ref Type: Abstract
Ref ID: 532  (Would need translated, doesn't appear to be much of use in tables.)

Ziv G (1976), Absorption of ampicillin derivatives from the bovine udder, Israel Journal of Medical Sciences 12: 260-263
Ref ID: 4493 (Comparative absorption of several antimicrobials from the bovine udder as compared to radio-labeled urea.  No concentrations reported.)

Ziv G, Sulman FG (1975), Absorption of antibiotics by the bovine udder, Journal of Dairy Science 58: 1637-1644
Ref ID: 4515 (As for reference 4493, just in different journal)

Ziv G, Gordin S, Bechar G, Bernstein S (1976), Binding of antibiotics to dry udder secretion and to udder tissue homogenates, British Veterinary Journal 132: 318-322
Ref ID: 5480  (comparative tissue and secretion binding data for various antimicrobials in dry udders)

Ziv G, Gordin S, Bechar G (1974), Mode of transfer of antibiotics from treated to nontreated quarters in dairy cows, American Journal of Veterinary Research 35: 643-647
Ref ID: 5004  (Comparative concentrations or radioactivity between treated and untreated quarters only.)