Appendix B:  Penicillin G - Procaine  in Cattle Updated 7-8-03

 

IM or SC data

Conlon PD, Butler DG, Burger JP, Gervais MD (1993), Evaluation of route and frequency of administration of three antimicrobial drugs in cattle, Canadian Veterinary Journal 34: 606-610
Ref ID: 4786  (Mean ± SD, IM and SC time point data for 20,000 IU/kg procaine pen G)

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  (Mean ± SD serum time point procaine pen G concentration data for 2,000 IU/lb IM, 6000 IU/lb IM, 20,000 IU/lb IM and SC, and 60,000 IU/lb IM. Cylinder plate assay data.)

Papich MG, Korsrud GO, Boison JO, Yates WDG, MacNeil JD, Janzen ED, Cohen RDH, Landry DA (1993), A study of the disposition of procaine penicillin G in feedlot steers following intramuscular and subcutaneous injection, Journal of Veterinary Pharmacology and Therapeutics 16: 317-327
Ref ID: 2288  (Raw data has been provided by Papich)

Oral data

Musser JMB, Anderson KL (2001), Bioavailability and disposition of sodium and procaine penicillin G (benzylpenicillin) administered orally with milk to calves, Journal of Veterinary Pharmacology and Therapeutics 24: 161-170
Ref ID: 4204  (Good oral data on sodium and procaine pen G in calves, mean ± SD timepoint data plus PK model parameters.)

Musser,JMB, K L Anderson, J O Boison, 2001, Tissue disposition and depletion of penicillin G after oral administration with milk in unweaned dairy calves: Journal of the American Veterinary Medical Association, v. 219, p. 346-350.
Ref ID: 4215 (Procaine Pen G fed in milk replacer at 0.68 mg/kg for 1 or 14 days.  Concentrations in plasma, muscle, kidney, liver, and urine for individual calves at 4, 6.5, 9.5, and 13 hours after feeding.)

 

Supporting data for procaine pen G

Volner Z, Nouws J, Kozjek S (1991), Pharmacokinetics of procaine penicillin G administered alone or in coadministration with phenylbutazone in calves, Acta Veterinaria Scandinavica Suppl 87: 127-128
Ref ID: 280  (A procaine pen G AUC, Tmax, Cmax, and b to compare with our modeling)

Schipper IA, Peng HM, Vincent MC (1978), Organ tissue concentration of benzyl penicillins in cattle, Veterinary Medicine Small Animal Clinician 73: 334-336
Ref ID: 273 (Procaine and potassium Pen G at 6000 IU/lb IM. Mean, 2 and 12 hour postinjection concentrations in plasma, lung, liver, spleen, kidney with no variance estimates.)

Daigneault J, Dubreuil P. Penicillin concentrations in serum and milk following administration of procaine penicillin G by different route at different dosage. Proceedings of the 17th World Buiatrics Congress 2, 122-127. 1992.
Ref Type: Journal (Full)
Ref ID: 877  (May not be usable, serum data is based on duration above selected concentrations with Tmax, Cmax, AUC data).

Huebner RA (1952), Bovine penicillin blood levels obtained with parenteral benzethacil, Cornell Veterinarian 42: 457-461
Ref ID: 5524  (Individual animal data following standard dose of benzathine or procaine penicillin G with animal weights reported [not in combination] at 1, 6, 12, 24, 48, 72, 96, 120, 144, 168, and 192, 216, and 240 hours post-injection.  Infrequency of early timepoint data will cause problems with superpositioning.)

Luthman J, Jacobsson SO (1986), Distribution of penicillin G in serum and tissue cage fluid in cattle, Acta Veterinaria Scandinavica 27: 313-325
Ref ID: 276  (Has Cmax, T1/2, and graphical data for K pen G (IV and IM at 10 mg/kg) and Procaine pen G (30 mg/kg) in serum and tissue cage fluid).

Bengtsson B, Franklin A, Jacobsson SO, Luthman F, Rantzien MHA (1991), Distribution of penicillin-G and spiramycin to tissue cages and subcutaneous tissue fluid in calves, Research in Veterinary Science 50: 301-307
Ref ID: 286 (copy of 276 above in a different journal)

Bengtsson B, Franklin A, Luthman F, Jacobsson SO (1989), Concentrations of sulphadimidine, oxytetracycline and penicillin G in serum, synovial fluid and tissue cage fluid after parenteral administration to calves, Journal of Veterinary Pharmacology and Therapeutics 12: 37-45
Ref ID: 279 (Procaine pen G and K pen G at 30 and 6.3 mg/kg respectively, graphic reporting for serum, synovial fluid, and tissue cage fluid  in calves.  Reported Cmax and T1/2 from the different compartments with variance estimates, but no comprehensive table.)

Os,Jv, J W Buitelaar, J Goudswaard, 1974, Intramuscular treatment of bovine mastitis with various penicillins. Penicillin concentrations in the milk: Tijdschrift voor Diergeneeskunde, v. 99, p. 114-123.
Ref ID: 6593 (In a crossover study, four normal cows were given five different combinations of penicillins intramuscularly. The combinations were 5 million units penethamate hydroiodide, ten million units sodium penicillin, seven million units sodium pen G + 3 million units PPG, four million units sodium Pen G + 6 million units PPG and 10 million units PPG.    The same drug combinations were given to 64 cows with clinical mastitis.  Mean blood and milk time point concentrations are reported q 2h over 24h, but no variance estimates.)

Ziv,G, M Wanner, J Nicolet, 1982, Distribution of penicillin G, dihydrostreptomycin, oxytetracycline, and chloramphenicol in serum and subcutaneous chamber fluid: Journal of Veterinary Pharmacology and Therapeutics, v. 5, p. 59-69.
Ref ID: 4950  (Tissue chambers made of golf balls in neonatal calves.  Procaine Pen G, 20,000 IU/kg after single and multiple IM injection.  Mean ± SD serum and chamber fluid timepoint data graphically.  Tabular presentation of mean Cmax, Tmax, T1/2, and AUC with no variance estimates for both serum and tissue chamber fluid.)

 

 

Mercer HD, Geleta JN, Carter GG (1974), Absorption and excretion of penicillin G from the mastitic bovine udder, Journal of the American Veterinary Medical Association 164: 613-617
Ref ID: 5005 (possible use in the future for direct intramammary infusion PK)

Anderson,KL, W A Moats, J E Rushing, J M O'Carroll, 1998, Detection of milk antibiotic residues by use of screening tests and liquid chromatography after intramammary administration of amoxicillin or penicillin G in cows with clinical mastitis: American Journal of Veterinary Research, v. 59, p. 1096-1100.
Ref ID: 4686  (Individual animal milk concentrations at 12 hour intervals for 3 cows after pen G IMM by multiple assay methods.)

Rollins,LD, H D Mercer, G G Carter, J Kramer, 1970, Absorption, distribution, and excretion of penicillin and dihydrostreptomycin in dairy cows following intramammary infusion: Journal of Dairy Science, v. 53, p. 1407-1414.
Ref ID: 5014 (Milk concentration timepoint data for penicillin and dihydrostreptomycin for individual cows after IMM administration of a combination product.  Reported by quarter.)

Vilim,A, L Larocque, A Macintosh, 1979, Depletion of brilliant blue F.C.F. and penicillin G in milk from treated cows: Journal of Food Protection, v. 42, p. 491-494.
Ref ID: 321 (Individual cow Pen G milk data starting 9 hours out from IMM administration.)

 

 

Mercer,HD, J N Geleta, L A Porteous, R J Condon, 1974, Excretion of penicillin G and dihydrostreptomycin from quarters of cows with experimentally induced staphylococcal mastitis: American Journal of Veterinary Research, v. 35, p. 1191-1196.
Ref ID: 5002 (Mean and range data for penicillin and dihydrostreptomycin concentrations in milk after IMM administration of a combination product.  Also serum concentrations of both after IMM administration with means but no variance estimates.)

Ziv,G, R A Saran, R Risenberg, 1973, Retention of antibiotics in dry-udder secretions after the infusion of several 'dry cow' antibiotic products: Zentralblatt fur Veterinarmedizin, B, v. 20, p. 415-424.
Ref ID: 6600  (142 Israeli Friesian cows were treated at drying-off by infusion of 1 of 12 commercial 'dry cow' antibiotic preparations into all 4 udder quarters. Preparations tested contained benzathine pen G, procaine penicillin G, neomycin, erythromycin, furaltadone, dihydrostreptomycin, chloramphenicol or cloxacillin in mineral oil plus or minus 3% aluminium stearate, vegetable oil or polyethylene glycol.  Mean milk concentrations over period of days are given, but no variance estimates.)

 

Abeynayake P, Cooper BS (1989), The concentration of penicillin in bovine conjunctival sac fluid as it pertains to the treatment of Moraxella bovis infection. (II) Topical application, Journal of Veterinary Pharmacology and Therapeutics 12: 31-36
Ref ID: 11  (Peak and duration above 5X MIC data for 4 different Pen G topical formulations)

Abeynayake P, Cooper BS (1989), The concentration of penicillin in bovine conjunctival sac fluid as it pertains to the treatment of Moraxella bovis infection.  (I) Subconjunctival injection, Journal of Veterinary Pharmacology and Therapeutics 12: 25-30
Ref ID: 12 (Two procaine Pen G injection sites with peak and duration above 5X MIC data.)

Binkhorst GJ (1987), Antibiotic levels in bovine lacrimal fluid after single application of ointments containing procaine benzyl penicillin plus dihydrostreptomycin; and benzathine cloxacillin, Veterinary Record 121: 124-125 Ref ID: 4867 (lacrimal fluid mean ± SD time point data for topical pen applications, the text refers to another paper we should get if we model this)

Punch PI, Costa ND, Chambers ED, Slatter DH, Wilcox GE (1985), Plasma and tear concentrations of antibiotics administered parenterally to cattle, Research in Veterinary Science 39: 179-187
Ref ID: 181 (Graphic presentation only but has a plasma/tears ratio for concentrations.  Only detected penicillin concentrations in tears at 2 early timepoints.)

Aureli P, Dominici S, Ferrini AM, Lepri ML (1990), Kinetics of excretion in milk of some antimastitis drugs, Annali Dell'Istituto Superiore di Sanita 26: 161-166
Ref ID: 4836 (no usable PK data)

Bengtsson,B, C Greko, 2002, Simulation of concentration-time profiles of benzyl-penicillin, enrofloxacin and dihydrostreptomycin in tissue cages in calves: Journal of Veterinary Pharmacology and Therapeutics, v. 25, p. 389-392.
Ref ID: 6028 (Tissue cage paper.)

Bishop JR, Bodine AB, O'Dell GD, Janzen JJ (1984), Retention data for antibiotics commonly used for bovine infections, Journal of Dairy Science 67: 437-440
Ref ID: 4928  (Milk residue focus with no usable serum data)

Boison JO, Korsrud GO, MacNeil JD, Keng L (1992), Determination of penicillin G in bovine plasma by high-performance liquid chromatography after pre-column derivatization, Journal of Chromatography, Biomedical Applications 576: 315-320
Ref ID: 3882  (techniques paper)

Daigneault J, Dubreuil P, Couture Y, Guay P, Boudreau M, Landry D. Penicillin residue in milk following administration of increasing doses of procaine penicillin G. Proceedings of the 17th World Buiatrics Congress 3, 383-384. 1992.
Ref Type: Journal (Full)
Ref ID: 889  (Very brief abstract with little info)

Dubreuil P, Daigneault J, Couture Y, Guay P, Landry D (2001), Penicillin concentrations in serum, milk and urine following intramuscular and subcutaneous administration of increasing doses of procaine penicillin G in lactating dairy cows, Canadian Journal of Veterinary Research 65: 173-180
Ref ID: 5679  (Same data as 877 under supporting data.)

Ehinger AM, Kietzmann M (2000), Tissue distribution of benzylpenicillin after intramammary administration in the isolated perfused bovine udder, Journal of Veterinary Pharmacology and Therapeutics 23: 303-310
Ref ID: 3854  (Model paper)

English PB (1959), Serum penicillin concentrations in the bovine with fortified benzathine, Australian Veterinary Journal 35: 353-358
Ref ID: 5572 (50% benzathine, 25% procaine, 25% potassium pen G)

English PB (1965), The therapeutic use of penicillin: The relationship between dose rate and plasma concentration after parenteral administration of benzylpenicillin (Penicillin G), Veterinary Record 77: 810-814
Ref ID: 5586  (Review article)

Franklin A, Rantzien MHA, Obel N, Ostensson K, Astrom G (1986), Concentrations of penicillin, streptomycin, and spiramycin in bovine udder tissue liquids, American Journal of Veterinary Research 47: 804-807  Ref ID: 163  (No usable data)

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

Haley,K, W D Black, D A Barnum, 1981, Optimal milk penicillin levels for the treatment of experimentally induced mastitis in cows: Canadian Journal of Comparative Medicine, v. 45, p. 239-242.
Ref ID: 6648
Reprint: Not in File (Abstract only)

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, v. 14, p. 18-26.
Ref ID: 613 (Same data as 231.  20 000  IU/lb procaine Pen G mean ± SD serum concentrations after IM (n=3),  SC (n=5) and intratracheally (n = 3) administration.  Cylinder plate assay)

Hogg,RA, A J White, R Jackman, 1992, Prolonged excretion by heifers of an inappropriately used intramammary antibiotic: Veterinary Record, v. 130, p. 402-403.
Ref ID: 4812 (Residue paper following heifers with field tests after IMM administration.)

Korsrud,GO, J O Boison, M G Papich, W D Yates, J D MacNeil, E D Janzen, R D Cohen, D A Landry, G Lambert, M S Yong, 1993, Depletion of intramuscularly and subcutaneously injected procaine penicillin G from tissues and plasma of yearling beef steers: Canadian Journal of Veterinary Research, v. 57, p. 223-230.
Ref ID: 4789 (Data as for 2288 under IM/SC injectable data above.)

Korsrud,GO, J O Boison, M G Papich, W D Yates, J D MacNeil, E D Janzen, J J McKinnon, D A Landry, G Lambert, M S Yong, 1994, Depletion of penicillin G residues in tissues and injection sites of yearling beef steers dosed with benzathine penicillin G alone or in combination with procaine penicillin G: Food Additives and Contaminants, v. 11, p. 1-6.
Ref ID: 4784 (Data as for 283 under IM/SC injectable data above.)

Krainock,RJ, 1991, Prolonged milk residue in two cows after subcutaneous injections of penicillin at an extra-label dose: Journal of the American Veterinary Medical Association, v. 198, p. 862-863.
Ref ID: 1826 (No PK data, only “positive” on milk tests.)

Landoni,MF, J O Errecalde. Pharmacokinetic study of a procaine penicillin-dihydrostreptomycin combination in cattle. Revista de Medicina Veterinaria Buenos Aires 72[4], 198-200. 1991.
Ref Type: Abstract
Ref ID: 6263 (Combination product.)

Liljebjelke,K, L D Warnick, M F Witt, 2000, Penicillin residues in milk following subconjuntival injection of Procaine Penicillin-G: The Bovine Practitioner, v. 34, p. 72.
Ref ID: 3145 (Snap test positive/negative data only.)

Madgwick L, Mayer S, Keen P (1989), Penetration of antibiotics into bovine neutrophils and their activity against intracellular Staphylococcus aureus, Journal of Antimicrobial Chemotherapy 24: 709-718
Ref ID: 4839 (not a true PK paper)

Manners,JG, R Stewart, 1982, Presence of dihydrostreptomycin and penicillin in cows' milk following intrauterine administration: Australian Veterinary Journal, v. 58, p. 203-204.
Ref ID: 4947 (Residue paper utilizing paper disk Bacillus method.)

Masera,J, M Afiefy, B K Gustafsson, 1980, Blood plasma and uterine tissue concentrations of penicillin G sodium in cows at intramuscular versus intrauterine administration: 9th International Congress on Animal Reproduction and Artificial Insemination, p. 210.
Ref ID: 275 (Short proceedings abstract only, no data for modeling.)

Meissonnier,E. Combined penicillin G-neomycin treatment of mastitis in dairy cows. II. Pharmacokinetic and clinical considerations. Bulletin Mensuel de la Societe Veterinaire Pratique de France 73[5], 269-282. 1989.
Ref Type: Abstract
Ref ID: 6277 (No data for modeling)

Mercer HD, Geleta JN, Schultz EJ, Wright WW (1970), Milk-out rates for antibiotics in intramammary infusion products used in the treatment of bovine mastitis: relationship of somatic cell counts, milk production level, and drug vehicle, American Journal of Veterinary Research 31: 1549-1560
Ref ID: 5016  (more of a residue paper)

Moretain JP, Boisseau J (1989), Excretion of penicillins and cephalexin in bovine milk following intramammary administration, Food Additives and Contaminants 6: 79-90
Ref ID: 178 (French formulations)

Moretain,JP, J Boisseau. Excretion of penicillins in bovine milk following intramuscular administration. Food Additives and Contaminants 1[4], 349-358. 1984.
Ref Type: Abstract
Ref ID: 4920 (Residue orientated.)

Nouws,J, G Ziv, 1978, Tissue distribution and residues of antibiotics in normal and emergency-slaughtered dairy cows after intramammary treatment: Journal of Food Protection, v. 41, p. 8-13.
Ref ID: 323 (Residue paper, no PK modeling data.)

Powers TE, Garg RC (1980), Pharmacotherapeutics of newer penicillins and cephalosporins, Journal of the American Veterinary Medical Association 176: 1054-1060
Ref ID: 459 (older review article)

Righter HF, Mercer HD, Kline DA, Carter GG (1975), Absorption of antibacterial agents by the bovine involuting uterus, Canadian Veterinary Journal 16: 10-15
Ref ID: 5001 (nothing usable)

Sadek SE (1954), Penicillin concentration in bovine blood and milk after intramuscular injection and its application in the treatment of mastitis, Journal of the American Veterinary Medical Association 125: 387-390
Ref ID: 5536  (Crystalline and procaine pen G mix used.)

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.  Calves given 40 000 IU/kg Sodium Penicillin IV and Procaine Penicillin IM. Data graphical.  Supporting.)

Short CR (1994), Consideration of sheep as a minor species: comparison of drug metabolism and disposition with other domestic ruminants, Veterinary and Human Toxicology 36: 24-40
Ref ID: 3834 (Review)

Short,CR, 1983, Developmental patterns of penicillin G excretion: Veterinary pharmacology and toxicology, v. Proceedings from the 2nd EAVPT, p. 63-72.
Ref ID: 4276 (Summary paper addressing clearance with age.  No PK modeling data.)

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 (In der doetsche)

Teske,RH, L D Rollins, G G Carter, 1972, Penicillin and dihydrostreptomycin serum concentrations after administration in single and repeated doses to feeder steers: Journal of the American Veterinary Medical Association, v. 160, p. 873-878.
Ref ID: 5531 (Fixed combination, timepoint data after IM administration but no variance estimates.)

Ziv G, Sulman FG (1975), Absorption of antibiotics by the bovine udder, Journal of Dairy Science 58: 1637-1644
Ref ID: 4515  (Comparative absorption related to labeled urea for different antimicrobials.  Not useful for concentration modeling.)

Ziv,G, S Gordin, G Bechar, S Bernstein, 1976, Binding of antibiotics to dry udder secretion and to udder tissue homogenates: British Veterinary Journal, v. 132, p. 318-322.
Ref ID: 5480 (Covers binding only, no PK data.)

Hekman,P, J F M Nouws, C A M Van Ginneken, 1982, Effect of Tomanol on the pharmacokinetics and tissue distribution of penicillin G in dairy cows: Veterinary Quarterly, v. 4, p. 12-18.
Ref ID: 4315